ࡱ>  mo^_`abcdefghinF<h9P aJFIF,,Photoshop 3.08BIM x8BIMxHH(FG(HH(d'`8BIM,,8BIM x8BIM8BIM 8BIM' 8BIMH/fflff/ff2Z5-8BIMp8BIM@@8BIM8BIM pPJFIFHH&File written by Adobe Photoshop 5.0Adobed            p"?   3!1AQa"q2B#$Rb34rC%Scs5&DTdE£t6UeuF'Vfv7GWgw5!1AQaq"2B#R3$brCScs4%&5DTdEU6teuFVfv'7GWgw ?ٍ߲Usk(kqc`9h?oIirP }Mun#Ylkpps=zv~z| yۻW5w^ꃬfa]9gǶ Z솻3u]:Lթ/Weh]m$zaW7'tg;QsV=76VeS>ϑv]e'ten3uofCw9gw.piZN+5=/O_ՕVϳ]#>k\.]m³]oşXF>ET>˷bkm7}wnV]2Z oo?#*7 >[rƸ̌*_~'oVF\>zg2 [|FPōE.Ǯʪ'Psճq1i*[nf ̹\WcfE/ɺU?igzb~oj꿥2=ֱPeNcsYm3!dk*oKlܜ /Ҝn*S0zon{2īlgcWus1FsrqhmV_^?źʜ^FgN%LPg_n_Ld ɢX Y[ ޟ6WUfȻNW2:L{vMbA5w=ރ= =%{kّUcGSu~n{n&̻=[)ص܇\E%BoɷI%{MuI%>{u>ӄ<|qi*nɹ,kuVS='_uw܅ﭹoȶ׋.evT)ɭ=,~_f]aܛ~qEr, H">_$8BIM XICC_PROFILE HLinomntrRGB XYZ  1acspMSFTIEC sRGB-HP cprtP3desclwtptbkptrXYZgXYZ,bXYZ@dmndTpdmddvuedLview$lumimeas $tech0 rTRC< gTRC< bTRC< textCopyright (c) 1998 Hewlett-Packard CompanydescsRGB IEC61966-2.1sRGB IEC61966-2.1XYZ QXYZ XYZ o8XYZ bXYZ $descIEC http://www.iec.chIEC http://www.iec.chdesc.IEC 61966-2.1 Default RGB colour space - sRGB.IEC 61966-2.1 Default RGB colour space - sRGBdesc,Reference Viewing Condition in IEC61966-2.1,Reference Viewing Condition in IEC61966-2.1view_. \XYZ L VPWmeassig CRT curv #(-27;@EJOTY^chmrw| %+28>ELRY`gnu| &/8AKT]gqz !-8COZfr~ -;HUcq~ +:IXgw'7HYj{+=Oat 2FZn  % : O d y  ' = T j " 9 Q i  * C \ u & @ Z t .Id %A^z &Ca~1Om&Ed#Cc'Ij4Vx&IlAe@e Ek*Qw;c*R{Gp@j>i  A l !!H!u!!!"'"U"""# #8#f###$$M$|$$% %8%h%%%&'&W&&&''I'z''( (?(q(())8)k))**5*h**++6+i++,,9,n,,- -A-v--..L.../$/Z///050l0011J1112*2c223 3F3334+4e4455M555676r667$7`7788P8899B999:6:t::;-;k;;<' >`>>?!?a??@#@d@@A)AjAAB0BrBBC:C}CDDGDDEEUEEF"FgFFG5G{GHHKHHIIcIIJ7J}JK KSKKL*LrLMMJMMN%NnNOOIOOP'PqPQQPQQR1R|RSS_SSTBTTU(UuUVV\VVWDWWX/X}XYYiYZZVZZ[E[[\5\\]']x]^^l^__a_``W``aOaabIbbcCccd@dde=eef=ffg=ggh?hhiCiijHjjkOkklWlmm`mnnknooxop+ppq:qqrKrss]sttptu(uuv>vvwVwxxnxy*yyzFz{{c{|!||}A}~~b~#G k͂0WGrׇ;iΉ3dʋ0cʍ1fΏ6n֑?zM _ɖ4 uL$h՛BdҞ@iءG&vVǥ8nRĩ7u\ЭD-u`ֲK³8%yhYѹJº;.! zpg_XQKFAǿ=ȼ:ɹ8ʷ6˶5̵5͵6ζ7ϸ9к<Ѿ?DINU\dlvۀ܊ݖޢ)߯6DScs 2F[p(@Xr4Pm8Ww)Km&File written by Adobe Photoshop 5.0!Adobed@     9`8 0@P5:Jp4   !9x1" #w0AQ@P`a23$tq%y pBCԖ'  !1"AQ`a2q#BRCs$3%6 :dkTt_翁|O8-eMZL.jk666k6 *LZ🇘|;;_n/ǝ;M6}_u4}5=I)JYqC+rTITL!D9"O)EUKzD(&FJeq% ͯ@ f $ߓ^w>a! 1Oe@l0:§C{)W.EY?w9AVx̼ش_딬sAnSyO|N/fh7$kB2̒.0R@e:JYfYj& !ܹQX3;4Ebɦ}v@ H3k31HK-Sj-RhrBV>I6! 3[SL!X&輱z@WBW+mP3| KIws,^( $UH벽Jv] W\Y6xP =ěLzS.ɧke.f455\TZmA8R1Ϻddgoݼ>J^V^4`2ġQlp+2m5Аp\ߥ@"w Bt"D 0:cMDQ6ǀk,`w @s9iZķ@Bn:[Ӳl894@.T@ %9IEҐ% ,@Hn" Q6@"ךl{,Wa6?x.r;dtC"{20na)@"L1k2b5V,k8+eJC l; YdR'zBC)#ߐj6i7[D‹]@w'Xe="W9o¸e Re΀>e m<@.T@ ģ|:I!SXq[ܢg'"ʌ5K2,'~u8NE ;8!)jXS `6!0ԍ"b_5Qfp$H",W0Xl>%hl%Ql)@aA i$y]մm:xԀI ,Nl5q6w-,Q 0eDMSmH#6b+l5 g -T!iF/O=bE=NG,mDbc-TM4J9tU|j6 nW$pL><98 6MH~Hd V>ƎX#1. sQaC@p(rVHƃ9 9 Tk6xvOuJn 2EvN$Ȯr?R㇝F)CWȥٵDaʼn2rC0%xRKN1Ffv^-$[EѬ@ S")MI` x5Ul]=/ MWĢQ;d<1#@BaI!L/ ͚)%&k,YGF!MF8.P2fjK5l]:R&sYgiX`L܂@wҞUX ŲĿG]fq@%ϤI; ϳ+/Pl^c0 $,Q CYtpP dC&'LA%0FgdA2 r,TX7BW۟]mf]Zn\Ⱦ~yϧGbKw#*)iR~Xzp1eL%[t=;|?Ps՞Qv==T|ϟgG\r][Zڋ}Ξm~ݵÎTtvR[wuywuޟSTۍ=G=SqϏWJ{RN}oV[wyfLmwzۃS4us}_oS4(>O]mzQKQ_DRXoUܮMi{oՕ4SRkmUW-EGcJwU}밸kGN'7Y>^%>on4cw޶I.ZAFmk*+Q>ks r8;+WSÿ]@_KprVk4ڴ7%*>T$|:C}GO͔ Fڕ4/lPlE|ysꮬ4D-e9#IK6>=SO+:1nW> LjaT@?5_{A&{ 1F)t~VF lb夘GX_Eh2ƓjX`EW fI~9‚dOʀ0bA;.<:ys{d 'S(%zH#L^lrBY$$vʼn K ɐp6GqboKV!ܙoYml( W6mGS.WQ](IR2&T9WB2U "dg+H} d@!%*P*;h|jYD B]"1Cw1.v(q. -b#U/E-g_ K=3X12/jjisgm6P#D>q-a!y97 Էϣ^XK79:nKR\nB&P{ŵ2a6NmJd<&3Nm JJs{]{~*pipK֐B* <`\Mڭh 8E$e{ ~3^<3j}zLi\ YZþvX-1u %w-3Wlw`K3,ȱk@g(/3Nza*w K5q$L Q~X)Hci i,B'2Jά4bǰ;L`{ak ^Ps3!,8\.`fqNcb(zH-_%dJ|se#!AHA]?Q1 %5o䞞=t Q鰒6'Aq~Va F0m"r/1ʼnȬ]9O|284TDa14qjf)'q{"LűDx/ +KX&eBG,3i{Mvcv0R8ȏ爅XP:ڙ9\#K 26a_[w*Y̌YL$͙yܛsSRSE8f[Lj|9`Ȍfɔ/$6' N@`,ZU5"Ed3Ⱦ')%8;Z*rAnU&WQ]haU r$Q1 %50Y㎳efQxay{B\vToV߄<ÝC; y4CL׵n¡7ax]0Z |ӽ^ >r=lRa443}`Gn>Џ0zCDuw!3N(=^J'//rSd$,6D1(n z;n? 2N(԰Y7ܗ?7XD~fـof W{BsW7郻8i?i,g4qP};>tUR--Q=[Ic}sN{7o?kXn\g| $p8D xۅ#omeɝzDK18#ST;0JU斨!n!ޛ~.ů]^|4n.:v -deN{~GˍJ40=oln؟]@8)a@eq#6@6hInTlP֛aSĀm;P(}npUě :Z{\yHq=!ipՇoo(E⃅wO!ӽ^ -XRܼE -k//rY+u~= ؿ -'4@ޭl6-Gj 86(8WTJ ҙuanĘġ .t6~YB|Sr=z35oK=Тj}Lv\7"㗹xmm}f {BI4KNh& MHFE+H:g7K' fٳD; d:9/vگֲ>iޯpXyXkj7wz::iz4}6cmYC.;"^4N󧘺#mIEOX%$:LFCR)L؆zQԱIk5R;{0k[6@<OI{ ,hBXR¬t@`J|%TMt)ˉ%-*@"lP"eD5l!0!cVPԪ 'lae ]#b 唈{vcsz$"¬]٘8ߣzaVw0+$ۘIQ褊GY9J!QD#2g/Q6.&hduHd [T^HIVfN.F%\"%Ў".~W8FGYUǞtRcÐsy$f ÷]dctcx 4eG R9k3'ucG%Pk"ky6玬'~NsuI~ozad8cf=v$՜0CLnQWr="5%cbJ!c wIk +*#3M1 =0HE1[Σ]OIsMjQFv'0i9Tyb|сH7>ndZr ϙc 5I+ e)e/ȋ‚nv2W #IE9£L=d:QO(X|w P&>ۙYPa$ꚙ=|ݘD#Mr)C.Ci@.c`'u[E;(ӀS'M*n ^6|[l[aY3r>-$QB18oL=$C̯ X8O[#֝ +%!T^[șJ5*6\{*F4kYr/4_WXːw 6aQQ[JX7moCĘW}Sr Mg]f( B;orb +zzQXl$܄C՟J){)iiU-5m5W~|8v[Tk[QfŴ7'\mL)*oLU*q SSz]y\yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķ^~%-ןnKu[?yķLW!SU4457:_h}÷ %Ծ3rJJ8FRa^Zӣg2-4Ȥ=Tʼn[* Q" oeu)m,2vru- !ZXrmsf.~kl.WL{\H93evwLxÑfAY@dRl !ʒ+%DQ!MUY%L=:% љZ0k(Ơd{QO &L?/X,(剺li'E=F(oy8-KU#*-clx-ÞJ'ɮ"th4BGֆdO*0)/EƊ 28{ Gt ߡ a \qcpD꩘0k*d\8^<9vp9N,g4J_4CLYX _#U LE]9pe(-⦚P d yQ!H9S};-SM MD:k.b 4HE(ȊfSlJRoo?!}/$9MDۣRL;pڜZc]̎]Zo4;{̈́u &>C_srg Њ ^>:MGŔlsE^uNFŝ* k"sgǜn8G)liv8 <@M] Dt7\qCEqd4LL sd EˊX\#kJbG$Vi;X0c-JrsnQT MܟMBu&%lXIj'-_q+/z7X˫7Rd0}swQ* ܑ }ҥ%g:+%r3=ayF(^-*+?eѬ(ʼəBςaJ'"?3"ľR,Q#҄5&.hfNgRn2'BHKA|FYd{Ƌ Z q[w^HK'/g!RDLK&DppȺVۀp(HbiK<1^4Ӕ6{*#"E.\[Fml.Ա8<FAGJftȑ*Ŏ6)g2f@d^FoeXbПz^gf?& J8.ډO~3B-kib\sL 3_| .NZa?.otp&wBTaBǙ?X8dJX)e@$xrb.ot6B>N+-?{| V؏e?Y&KˋsmI4@ITdT4 qyahGn $ FU^|\Rmg|˘aPb 44<ai47/䪂 א ?Fᛉ$1[҅=@&Emsuƴf EA\Ո.nbl,X*Kse@HFx `JԊQ£ıCa,PWٵEB/:Y:uh,*f|$U>**O?l6~RyW2 Q*h0P2֔1 xQb +ӗ5Z„Z,ciddl+5ZTjjNWx A@9Ğ|jfxdBO3e4qR˟Uʼn.3 1/ GÀR0ND798n3V_O @9T}5 Ma 0?ksm%4jGu0r]HԅBO;$~8Vzt-dY'%H%qG.!H䒴i" [bpD/QI1"+SC:4+a׸H> W 4-Y`,9l1Vă!si3`ȷ0U1b!T3EaIdf !jyTO4Pv$oAlBVh:NuQ\HnV>mw\*H## .ƃ*NS]LM#9QAbXٺ{[UhY gA2MK[ kqN1Dnb6 :BV0 <-jW#F: @CAN1imjKyY%]I+h*I<^F<9P[Y0J2H%Ug=P-i[L-59.dtBbU-,{k!tUZx1\20Y2[)pjPqY^XVKXE`4lD 'Ñ+Ǧsj_kMmZI`CU ԋ^Vu_{_M;Oi 2H$o`BSJ`UO{{ABy-^I]êHe-#;FWR6Dq sz@zEAST.48c(maϖ9EPwi{oV)%[@x`h#1wRA{Qx7L`퉧P3Gy5H5Z;QGp팦`Rg9j|-Z,3C0]w^Ye~j4gr \ȵ퇯:擧*OZ(EHuƥ {lj!.pF4PQ.F/m ;KT (c;UxFp{Fw<1G<ij*IS[u[}'XfbAA#ԷY<"[t`Br*0"ӭWlm4hw}ꐇi;kxZWl@,h G>P6;MmGtCuql#9YsUMs~Xw"YIhc23BAN\rIf%>ǯ2;0Ǫ[r. Iq ے\dz4b?uUef hkǧudOi$ W90EC9l?[׮AaouiQݙsBzhxYݩ`qFanjs>KvcE?me F^ASMC8ٌw%TƕT~"\MWiͿ/mK9nň3-2ǒ޽vzṴ8Ez,JS[1\k"哜w,chctl4F結[K!`n`p3tVWHգ0dmD{KT˔S8UUIffRw;T~ԴUw ( T9DIQt~MJ EP]´ƔKIl|l\#);/StoJ'v3=\F4*@ۣI NSC !^|ȍUOy/9VWx+-@sow B.jK6D딣妺Q`1ʒ(w!; ߤvaPI`oQ5b_eI(̪n D=C蜑&qO'{}ZQԛŦ^QX7Z0 `1<&xӷJezez>~V.6|xW-_3vE+NLje< qY#Ș<)qjw,9M%e($WQϒ0WEcNYuMygBaujNOFN9+LVY׻VX"g7T>=/3wJ5X[ly=bW.UdӫAx%E$DNv`Mۧ3+A)x/Ph-:²cSoš@ΌνΞ)^Qg~mzf4i"so6mhEA7u„,ae]ƫ2:$w?)Xͣd;>!D"8Pwv8-v }WDᥤSZ\hATD<)1DGOXt3Wa㭭cٽBʛf$rtNrPJ-uJ_yNqI8VCMigRgBT;qfw1EV(ߑbQ #\˷ӚKOΧԘJȻMx],\&zU3HI\.RU8WJ2K٬O0:l5!;pb$D?:CM4}}5dJG дX~&ޜ.N}rV)s‡ oZ}.|٣\,7ks. y,Ii˸1A]uPHU2"U ^ @%{:!iJ" 1D@}tSb1D(p1D;,iL(r P@НC2`!K@ G:G"7~!{ =?THU[#K@kbo .<'0/Unag>UOO@0;83r<@N: ym-F릛zq"D  ~]lJl|̠*qWdAV)wD\8P@s}+--Zw\u4>.Y=G-iאM,VR~j9[)S2T8JA_)?\X"Z sڗ$PM@t5H c$勶LOADHs_!^ɫ@Q6]Nx%X{;6*-5_"i$cfl0oFEyvVeVQZymrzeaMe_Mr-7so-wP^f%PEr)l$q|sw3 SEET3q4vY֭8AMZJd8%𚆂1N&op yAlgpEFJ`nVgO:\H&a*Rp i/häd5}Pk2urjbNl>ĭPHbJ<|*QW#;ΒFȥ&}HdD.sBs?݅Rm>, -HYUlՀzO CMb *x@|:/?qT+\|*{-DA֩K-x`Hnb͉.ɻII'w;Ɨ-FSqq(W/r99vQ.MU|*E+,ڧ n%$z][?E+ʝd=tRiQyzަYu1bkSJ0]\Zt$CCDF~"{MƠѼݎ% G M䠉6o.sDDF>9UοQ6Yj$HcLZ 7G;5R3.Lc7k31Kk)ӤRu+bP@"J~g%3ۃf5DE)8B5h.(t$CyQ)2(\?5F۶9䈞HΩ5|RF,r,ͼTL*p<_/0_'FV#%fMY0, < ES>ؼQqFǰbɼ)NB8#S2 jc 5ɼGY@+uQ`K!䫓%@M.G(AESiɋMj6D[CY: eSM#%#ށ#ԇnUKEk8wjC+ 'SϬن^]"dm32O}7nE ){/gJ#8BȜ"j:Qz#">h7>.ɥB"Q38@ZK…*AUWݾlN`H!80 ̖A,+ݴ^-l@YTl%S7&|vLGУ*HP$Si HH>~_2$ HZ$o0]ρo1nAWh[TJ>otSxA4LA{# )gZfS<+Ti&' ͚׮k{2Iw-0~)hNGM)]1Cba3PPٴLp"}.s 졇7y2HYY<,fDbCi4*o"SY3SѠXE偏!Ѩ8rjvM O,bL+@"Q'׆8Bݛ[)tW&Л[/h_֛ro_$;f|@¶ ffs7Yxp;ՐD*bbJQs]mӲXVǿe[UF`5nͬR0uι"ǟD$ALިlg;Vflu$E];rяP0%UD((ugԵO3Qޯ3񕊭v4L9i5].)*Lc|.1 D|UvkGMB%鈤7\A m;GcAt ()zSmsN &!\ P _tMYf#(DZhpr­d5FYVg|&/n߰mBJܢZUɟYB^̗UrcEE{`<9dp(]DZtx̙S{KN=©:z4:7#ӱ;B=SN`*hEϛv12@"H6t* >iWME+w,U%>z{dI%"9+WMm"18D2V4i\Kx&أ>!Ϻ3o/kFIsZq^(=rHPQv9I{M8j "1C\npnI"hs6wOK<&)0a NTHIJ1xqee[5l|mkVifpD s) "nN+n9I[# dIpJ.WzFV\ْ e2xaOarLixZfl )rœԄ4-Q"ܼ/\Ona5jLW3wy8_SU_0ĀPz4x7EymFd|&"^ܴܢ (ٚB>7 B5|6pes bN2ڬ,b'!vD2D狀{\9˷<*xJa3 s)m͜җN1oV\ng7{ 뷛jf )A)7@MB$P7X/.Z<Ӓ;LYPUrf>R{>NeZ39iyV+N b3 h w \> + c $p259 I n0v|>#&WprmMcֽT5.Y&$*|XO/n߰|4hfMdc6N9 c!xeJJc&fD?sݿ~IFO>Md]&5KUHLNg LLQGT-oe]#rV[van e$QXl_?n/"ݢc %6kxAWh@B2xy.OC 0r/k`~9'1vp:4Ef-˴p̜Ş3I"ǽ_!ݲ:4EXƻEN*YpjMkQR]) < ,j"FbfM\\{r˽| 0Cv1?&9i+ LbdX7h!L/po] =1Q!u VU"10WV3C %!(%8v{٩gX.Zڵ@SJ-rq1)x򤐪P€\*o>>\~dr^.;&q@1@J`ͥjW:{S"][.zbiE2d"9asöxgN+]R5}%(QSLhk&2 b6;g!(U%TcuɬjrgFDʙʪ&H1O)pf|B+-IE^J~>))c*@ A+?5x_irtFQ|TӟUdtͬc6\GErxU+ܦ(Ǖs CcV Z^_fV֮f"kV8#EꤺnoAΊ>iͬZ3H}"pTس^]Fѫ ٷ %fF%رBT~މEGZiKAtA( #rc&ٲʧ+oݬe٥9RFəb6E!H8"~U(a8ƯYas:}{zhs3AS8d()Q#Bʞ-wFrMxe+`sEa˘ZV J ^^}ɤڒr) pn̯&HyF =j]öѵFFpSb+e"L _ MeAŅY g{ ~gyvu )ǸX"lqߦ.dwo$4s&cD;5}׬,sڗVЧ[L>iȪ8ҨQT|fLo0LD%&9sZmѭivigV+dGpqQUI-t$F_U,ou$S,uIDMCI:R2AIdL*(uwegZ4IXj 2Cܲ&Bgk^axg!`-YADx٭knʉcU&OSRp"Bu֛9jS{>!DMN"X8ؘщb(=G$xSnV;W:d.ٺnNMV"7T)bo0-@QS~\ hd}p ^gyvv2,%d7).#htB51r  ?9\pGkhz]H>H­U9AUU|=]9J\La^O+E٣lծοDyՇ QxIQOMZM^g՛ #6w.9Tcw$|팇o|;aO{7{^%lM k޽I],0Eh:Eb-uxԋ ,Fr/lV#+f5Heŵ\-\{GnMjfTC=;&ܺZ~?1[e?Y f,+AQb`ld.epPx˥8UбkװˮhD2IeY2)|/9~rr:%Ż7GGa`at,MnlAdY0F <Jx90,WC8mޗA(Aw qaƧ:9xm3|c4+KIRLMA)~U+͌tCJr\dBb1$d QpYi5`0F6bԎP,Į;]57U9Bӭ:nM9H[Y$[b(r(=)?[BDomuw$%*ҬvYYpةWE: WwTMi凧uB27}e#,V:4 YX4L6 iU֌{+ ^_9v^\m7vlNe(zN,׌S4p -8$g7YM\9+td뚿k_vËWDJJ"P7n!p;$9y^ɭ*6y74%&Osc7TZ$X&:F][aOWɾ~A$R%jfBƢ~`#U9*g'^2<91y6x)մ.Z:,Ρھ>jeՕh %*5u`p V1зZfLV.P{{"dx5@e\Ba8%xÛn${̲~@s U]JJb% p( q<ЯSbL+6cM̶YfF1͘zU_v j"RPXgh]B HJڧq9ju+bvU9P| Ⱦe_HYOG<+=Eys/˦I0EA螾+Dj۬iy9*Ɲ5S]"B&]BE%OkתOuק`5 aJN^!0G8teb$'c%Xi -効NÜT" zLp* !]p%kY{@hd=gjM5z(xcJ]e: ~7Q(3d0wrm˙ e2ަ8jENZJ>r# SG)I.3n(jLm"Ò&@c?`$"߷zрH:SۭOSdp]pDڳ%T-e6l\vO$jܥs!WY`9|͙HjXվ[8fIuUjv<R*ɶFlt3xC7YKPMJ%PN SeRg{̥6+>,Ul7%ʴh)8~hH0Q $jDU&n(R&Bu^]x&9D1i4X2rYʵFHv8{8 .w{߷֪:ZWryi"1)"eKuYx/cU ,Vvv?67oPgCW6J3.C]belVzR')LO.M3Ad@wD!5$2J'y{7Xu2^^F4n.m( K$Sj)>-"Z ã$w%ZX9IQ@X 2rrA7+<«UM 67l[}Iw%]`QHyy2GJHHB[q?5iL|JF6m ˷?%r!Ox9sv k)9гP{-(g ddYE]!sɍ[.5_w7P1eֿtcV\_ɶYJh3D5Fn^ļOY:xRorF\bDYŲ90luQXjǦUY.G59cT*7oiZnYŗIU&)} uke84-~՟q Mcg#L͚/ Or{tq*MvcULP_R_u:qڛ>iy׽:o]tUY,bHD(BB":ڤ/e_5xRخ"6wr疜vY:}@: fr3Kd&GVYi~,I@X4!Yn>Zk>Y3&e6i:Ǭ{\}9Ϸj&48SlQiX+hլ(b eHtw9Sйlõe'7="[;oϧ8o1arfbD]#%Ρzw*x~dgdU}-#%AŞ΢咱Ϛ T|&/ .ZL-.X쪬.WE8ON^mRvEE'oTT@:y8ܠ4RQX OW"zN7Ws;]p*Ŧѡ0 Àl͏;xbVm%YuTD[n/:VCJG/ݲzD!4 ![،YoW=UjJqW^0O 'I z5u9PwIEV5u\4 bDYD[@NJr뎜],F.;'i{]59d5Q5A53=&:bej5Ĉ}g/N,GR DenS@)[UzvL;.q:5<n^#q]0#R$=$eH s"=G@""{:uH" M%Q!)D;^͙7ϖZpr>Oq҉`)T]ND8 E&)5+4M5Em[k \2-pݺN\$bxðqc4U;]r:[u 2XERiw2.-r"67N_ǓM~!)}&ZCrɑ;D#e T#l#+@_AILn/Mw܋6 .@(YTg sHKiZNMZavsݻFR2(s!DD@\w׎0l~ ,z&{:6*ď!:b\Y<.YQJc<[= h&p%o ]T`a"&W*(r fmSP9&&$z"GRͮV%R8l2*BxP ^6-zny/2j'P~в Xwm;[AK̙COi$|=}W3d)i@fu+c[,(?NX.2oQ 8zAECLBqwNodD dUoŮm s~' \X,'Pl}Rz9τlMw[:S>YL/_N5[+!v) XPEY-¬ Ez7)YX%|ݫ䕈~F*&E1ȫkXYgh )Pk{^pc()hV({n-6U_YҦX2,<r24B_p^C4tdH[qnEĵ鸈vH/KmL9cD3MLqV3e;iS=I#{>MZG0x*f!\. aG}s/pnGr3VsDU -]p ѱYͶ S@CdeSENCn}ca76f(O-[k!.P ܦ(dD@?XoUw-xuOle'ZTZUgqnj2eT8&UE20|}z? zc/w:%r$`(J`hu˜z*FMmN}R86h-Qe<@Y ]R*(Sj*S\8Ww~P}gb\Eg˔(yWBbʽ-gq]\xT72jAS_b, z+1T7r@UuB ^K5TZ ;Ee ?\t t)FݖldX4*t -VnN+\IcJFmEn̑Xg\Fs\ΫT$ N,(,#l 3?^bdu;-AëG.Γ^McՍ%H^q<)!?C.r%gw3L[S_3e_JRHxٲOB:CWn~2_u:qڛn\rd:>8řU;YB^bEæ&!<)(o7rfVFD33l|w$U%$zSdz"g@#VpB`arRZd VYnDb{o'ѫGJ:B̆#D(); 1'O^IQ"GՙWڝpxЈ>LESJ]t0`ꎫaG}nGpB8s*"B#q`o=qo=a9{M 2*(xJ#ndrL<5 Rw):7jf "v35.vXd#ϒ["cg*/ Rf0OnJAH,][%O_(,ׁpyʬSx0J,lT -d a+FӱZ5R{)0 Y'1 ] 1٫I-\ͬz 3S++#l۫R&mTIJEEKyc*vW3twSQh@rmT.ԫ-QTFP B)DR߬RK`s.IVFv,jc2U8ЊbApya.J&0&K+1 Izdh6T]23Mōt$YS1%)UAT7)spױ-vz.v rԲ= YL䃍UT,WQ'RWds#`iM /\2'|@)D7+5B:F*l-떻i!*Vm(*Io(n#i~gT }6Z4[!C7lX.t8) S> !p|wcx|)pQ+bj\J"z݁j8JTG@vRx9 3"BrG4 Ir4O6N:M?+DP<@l E1x=!(FeOfNlP+=(I * (D3f[nuT.ƳP wf,'URE.WbG:YR냙$gvߧ̱ U,H˦_ vA{!1ڎVR}SMr*d}N٨I{&mQP)fR@%M+I2LqaCV'W[nmAFG~g:\gK~dzA' Ô_7u\.'Sf=ha;xLJ/rrط8f5%?3%$bT]j[xfQ&C1(VY:ַ8hB.#$>372 $q+\>ktghfY}h=8ˍqVDdoqLLLo]݋Ʋ4.z#2i~Diݱ?O^a!p ""=^:9q VX&a iD9)D!D/\6OӫTu~dzAܞ0TYoWAm5uͤݨV,a >JP0FƩC=pQ6Yr.<[VNFp b$Պ$LHx>bw-NaljIDU!F{A'ûx|9vxB<_Oۈ1V/UÈN7A|YԎ>h C 85p{Nc嘿οDyDxE7hFJU\u;~Q^9{L[(Ϟ.B;9]D tUjwn)}#Ö7)Lb", ǝLRti~yM8XG/r:)M0]&GArm6J7:%Fh>Ug03+uS`E.οDy8?pp~!DxД)J`hv8unP#8'#܁۵@ek8vBMqU:hBW>P^73;e5>yK_& bBYD84h鐆TW6ԇZ(~{[۱M@NMs v7Boې=nz? z9ƺ-d}6%G2c<]*ȯ3V חrᝡ g`]qVc1l:A{Hf/p!գ^mlMNٸ`lRJ@yĄ]EG*G [S1D@}רnnv/%aqL@#1/!Eh(!1UQr10l>$y-t\PŚqI2њdfO 3Bb\-&!;pX O,D>W?|9 |:/:~=ԏ)#P9Ciy"`!SM+WH$Dۿ!|)ntv ^5ĵa!Iw L7XU#B=!'r9r*DfaYF.. HRŝB[.#hBM!#sՏ^銉E2^;)TY(rGr Byݓ.3Y'-֊ iwtN^0Ͼr(Mc&}"f+uZYظlo'[kd˵tΎs> ?qXpkF7IL+\A%0ntU KE3 Ɓ.9-QYiQ27x"GMC"j*t~U2Pc]ʶAVQdt(*{b$DaeANW3euU"G atYs~Xv,SDI,DM]9 _x-aKSwVVQgN4%"[*J/*O&Jsx\f'J P(*FWyps8UB,,X !~~Y2q Ìy]yH}`|2(HzD]Eb"#7}J # 3Xs {dT#ʷ\K̯j#If8{Jqfґ%ƧmLB-%^I9ʶVApy@2){\/,N *)99bj!i(6=fH3\G:jr%pfPe*RJ y#o;&!<лfIxHE$)}F/ɺק+ F֍e_ 1/W6<@ɂ B ]'vOoa<πD3@waG}nc{8`7p8;;~dzAܞ@2pePNW9xy€ Q0IY*ոOWU!!TֳH>ADZA21@@@@8(q={=l-ZUQ Y bL>#}EC7?#θ=h^ł2s.v]T\g]i.t^*1C a(v&?dܣm&gJW-ׇvX q%:]27fC.ΚDɘӸ(jKkc3Z)22ř1J2!|D&P?>[a'*ih"s&X.Zb֋$[hGD+Z#,b&CDg.4[4d٪"\4Mʼnc)!̪ɝNH{&M,ĎJO;{F^( ooЫdZIaEFI(ͪJTΨIMNN˲giJT#dM32P% =hK۫:Җ VxIīSurY0dJ 䒜%Wj]ƵMNTDˤ.$Y!MTY:YqAӎ,_T}N`t(sX71;#lT ǖvO5aH*܈?&*p!}PywȢ[gVi)dye-%\sg QHfY*T;GHwHؘq~fڵ7Rn9|}mwr;]2Q YHN04bµוm>ɁhY%f3 "^QO)f[rOS9MRnܢY8}WР9ɢo10̚ŶjY_vRJZ=rshy>]eҳRl<e*&L5)7,#6Ui& Lz`YL)/Y$ky݂ QrH@˅9O/M^7{ Йi:S5,ȿ11Jŧ) ="FeN3G8FzbK"q;۫1tJ:6: W|X ܻUOOM!zJrt¶Gp2|qlX,ƯGZ$vszsnZ9I4Ġp=[6z33i40vIqoiDF=O^9 $c&Hq3s6ͤM*?Y *\E%H)ލ\[JV-KE2sUNW,t[kIX嫆N5PuˍW'u {pP5kR*QMk5o#}41v&6eg= 9CHyc-ͯ^`2u*LJWZۜIx1zt:$ 6Mӛlm Uj/u%jKFJE$Kb9tc'%ֲjRY )QQqSG2HN!fUNV {ΓtQ6kL;BkA=BIt=ƫ@gGgkP"`s+}˺{CW)9gtFutQHԊmU1@Q,ȇd J[ u=Gr Us)yY5HsNQ}RBMVR(DP_+u˔>9ܾG9~W;]ЪRƚHjN1K\ˁ:uͮ;ڡL5]hUQ!]Vh<ZSG Hة %s@urό|Qb{;eRB{}^Ԥ$\ eng5Ye +r7=sx mgx|j[3_Y#]%Y)YR6 b3_9n\XDUbIfIHw:lADQ5,T˸_qsj]"vB)7iok]i1֙U'ڵsHڙ$z禚BfӔ{iW]зV$k-P]Z?hR,t.tۢK|iC6YJT!W]h`b|S:r,#Vة1mcٱpnڍV۠]FG&xJ( ޝ+oT2 -R^bI2F:;EyrWiܼF=GϚwMSK7m{CK{|nj >\lj+9(nc{+q+5mi7U,kȐ>vNE0 :S?O^2Uܓk49%i'O ^@rT,fx̿rq?|]J9;ʞ G+gxb%v 'P3H?pj1PBǟ\kd@ x1o3Q̣CFȜ;*[$1)ᝮdՕl]X˳-x 2v@ajqEv] $L#"6G"Lަ6i¾C. +6Vc%^X hTLKT/+2_@2Trlmk4ښU&N[hn ˃s=WDg9S$HZm'+Jٮv4jLÅ.$Rdj%9/Z%},N:v1#^&VEU+xE@}AxITnҶ.dv5S*Zݾhbg *)獞z tAC9 56)Zd"& ;wiv*F*^ [bw"!ʫAlQz3yJnLף#sӠӿIIyA4*vlT|斿7Gy^MWl=6 vv V5hshxSc41P"=jg+=z#T)VAG!!̃ɟ^}N+,xBDyzd1]VoDQrdru|#H?FsQI˴n5 5 (Z +)(clv;fC\;+,ki,c5zR|Eogn.4Qv۵,y]5vE2YM5V?Ay^bnE.K;V.]Z0kӦ="]Kz[:-kޡ0*v*!1ҌUGEh謑17vqǧbT˨REI^Qf/rܳfl' ,¶ YiE3I s=oO@.-*2S{,+,U.O sN_P+O*]'r!\ebd-o,Vg%jeU&?Pf:gzOypܪ6RyYHzcu3Q1=}B0o ]߼洴&7ږ7lb4%wx::~BzlҲV>ld\P[ vޕ\вQr54RT#e.3Lhb6xStHG*8OIQO"i53dE2koRfZSeq$1lNWȃ&gm(&Ar]Xs-OTgKqXEC-3^MB>=Q{mw ::Tƫ}OgNizˉ(E ݭQ2#yI`pC7+oY"\ɧoGUQw,-%qce d.9T2<ӷm9Drg9qpGԦu:kIbbHHmqM :z<{FQ~R?wD<R5Zz#pT_5Q̳u MeWI:#BUP\nqU :F8ɸ 4'+BBCR޲ jga_JY"ncl T&B 5'o_1JSڤ6Zl9M)5ZJ*H#ZQuqs&\L=j:[ѓ>RXrڝb1lVMcb;βꦣm'5]%2U&/q\ z56#ۡpMQVUbN_4~wHȸPb5ߑ:m^kK.9lDdž^}~)hff>v ʷ"u=[[0ڭ>k9xЬ1RnGRɺ~:bg9M+F鑬\,/ -װ] t=jM͸+#W, rշy,0*%lUOx%nc1|?'_9 ON\M9/_ vM1Yi'蕿x/k<ݲr͕X+yGV׾JYR%k/ޝ^IU7*@=@8Cr d`6ٽ*R=D˻mV(T"۪ER=V$b8Y_۹qCg9_OHD`ѲqW i%$SM1PxKjxj{lR]R]=:ٗe텢y]i% \r(ͺl.r"ɨOr^: ϻBC#kJp,r0 V (q56'xAz0$3&)"T]kDUZج4iޠ eOq VNqX^͑8"rcfe3tL!ˮY.Q!;3\hK.6"EE7T Bw&Ơ3@ɭ TrozRc3qvG>*e/H1m{֍زo*SI1(xalsX>_0h'JGj5PW]""hfcZ{IvS2q3 \@1IȢj1<+&sWH^[Ii+\ vמH7#ub> UAE,DWO[Sqyrw!'\Гw+UxڻBǪGI, txÒZJOiǜ.]n01zVMn-I)¦F~Gȡj UMN>{2YGHHźe4gH(@m^>gI>1Tݿjr-Y -"1Johl\FMtWbY& :!r'$gMSpĪf( = A7h*GI&᳦2Kp:K G)"y=>2AF06PJb ۺl58`!O3 ԇ>-"KhZba;?|5@J1ZEƒ䮑9lƊ7HUD1)HtڨN)ۙvpBGPu2ЫҚ7B7@\MecK eCc:>RaD{.p's dԥK-ڰJC^1@H`I$ȒIe)M2 D!@ B_xƋiD[bYjss5WoILUSS!J>X@D6+88q"$kvLL= P:_b)H͜$u^clRrqٚS=XRthEN @V+!l,lPe@.dHs@"ޛd Vv[7L ݺ ") B( A7h*GI&᳦2Kp:K G)"2pD0E!>@H,h%PP7!## jQ3C%9C1G:F>-8 ݓȳh(Pl܉U a;?љ))O_;:'iWZI4~c37ȩ$D3طE;tYA},=IЎU9.ԥ!9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.o_n|s7鋯>9۟bώ|1u>~~s?qL]}ϟߦ.oHLD1{0v:y7NlPWk4L;{~,rScjUޡj+64Ȯ]ҕV'6T(%9e][lArڽ[95 ߄b{Ks@e R1]~`YP(*䉬`aؤr8(Qg#(UE0coN~bU2О>=gCm4 q@x*:c_X5$l+WmXyl0tJޑL3dҍ"`cޝf niIg9;6%ٟi1rw1jn7b3Sn~8w(rzƵ4y">dkRF >81L~G4.驚oPerLUv锡ӥgFug>覙L>ޣz|=yxb2l:YXuQLLcsIed]̉iv8]8uX 9fN,Z8l*tQW/XB/W %keűoJ}`$=јB>Y@Rg2QIFM8M'[.Z"Mp*7E >nTXRnL&3.2f(FtXlN[1+VȨIT5BmRjiE+Ae{D~[?c +2ݬ:q-Ȟ 5圵EQcf1L\5@V%ʸo13Zq b褂v̹c"?Bfjt'g+mZUd@*Qz;@Lb[z1[uY9{#+E1,Z.Fz RMu&<ْcB'n\=V},-=/XN֚7Q|ӹt$hHP'1y2Aקǣ,ڜ*FAShwS adhz[8kRZ>]bK'gכ($VZB¾3qx nțx+?kbW,E+Ή/aN*)vAɥΎp44`عxQ>|N):@ʭqEBf~M$F͡'wj܆"o$ z~zp{u㾝T ³ucX:qb,*Xl#lXQItT=57&8q+d K~yZZamCqN<^,nGNAș[qYr uH)N|һ[vyˎ1|FV|MMV9/Z鵛zj\<ődpQUJ᳇-y5_ZvY#?[){ʏ#UbggR*ԼwQe1/9m.YqՄW#ݨX~>Cg-_6Aߥ0֘xl.ɬ<󘚆3F6YS Ch,[M۹UTTSXneȌ:uBu UUV2]UH{$1z1 nJG(qڝOGG25 Z*Tj'jaUͭ1ҭ]57U3w`t2$ˣQ /#g m&P@,?(v8 љ5*2(E)t YiK2i&:\dHY4Q߯nESz~TUE_ G `"iᗥ8RKhc{b;bbtZHT d! !pHuËg:~^e6NY3!g$ŃߌEVtB`pQ!1Aaifbd5qUH!Y=[;U2%*%ROq♬ɯS{9.нYÕ,K%" e35aԿt+E=9ZAAsQv#Kt:?0yQ/^u԰ls'EJҶ}*ˍg>򼫗b۶ue4EC59]Z^?o]GN׊饹o,k̊#&0 شۂYɸ# sbceE(̻NUSuNSA0fM74ąd>R=M%j\=v:ƒΕhb gZY"gAG$u&ıh* uŞ]]XTظzek=n]rn5ē=*A *@,(i7z Ǒ|XT>eŷӪhjzj!RE۪ͧbD(V+p$ Nwp h' dVt|tVD-1tZϨ?:}l#FY5=6ڳ=8SLƀ{z&vl %Cƙ^fc&ȼkYss7P;\MzI5)H$AîpMHsfM3\3m֦)l ,g7H E4u=<^\$(4ZW$HS2k.jWp4:ؿaJ^xHiRo/\P,j<>2.Ed(8LU,C1eIL?5xgO'a%22/e7?;ROT M,1TYHIBA휕5 r )RroD5f)f0Z d,vΕhU!AouJC\*/PK9E )z#-j"jY}5C), _g0(RA؆CNw(ɟҳZӏVFtY]K/@=?ognS^u܂pr#wlrE}23fIBHt n5Z1]vd-VVMfOk3x<DU(mX*ѺfPVSsI.îd(W<]L/Afe:Uג0G;$Zn/ ՝.Nv&UwG,=ɻ"rSu ݀8|KVOE/͖xUX`]<}Zv'UOȡ#Wh%X&vUbxgԪȘVsz& ƭ (3BiuLEɽ ⋳HºwV">mƼfbG-cNUwUOLmbTy & 9)$LX}%}A2̆Y]ר[&fflYGAG6dkdw`P7%$Ϳh/$8MWl ޕ5Zgjq^FAR9gzLauiפg?2lΞk.83V$F/?,xyccjV(dNYC9P!ڸNr77Պ;fs1UKz1Wը&_fliUeA+`P7%$rHۛU;nwGeAi'?K_1ʣ C8nezY})1hv].' 2yDJ"PP =[ic7.Nx_Sf(ՄlkXk,B^&+ (.yz%zda#g6|g*(7w0Z4Lc?oU wԖnE|;I0EMI̬ 8_A@AecnrpmWIH>08٢['):CnYf PaYJ#8b嘙U\wB#4;wn5X0:k\=R{5BDI8րuE.ÄfNJU CsGҫ&gsOUfXWBIF%P3%I˗.z )Udtk<-3WK5s2mdܩk[g˃NYC[W);Y rzZ!Hџ ZzE&%f&E_*u֜P.^AZSא- 2.qKeP'ߵB̵cnc뱲sks4dwZ2 VG FcJ-,LD"xU+{D-zb?#Hh3uKKGAUeዖbeUr߬  b|_w+ܴYFɓ,{^QYuY5 \IlY͐*R9A0) c덤Ю:=Jj)p&PM:!#/P[ȕ! 哚rKI:/_k=;vLX;Ng4'WI,#cBUt (3nc(`MDii{s;96"{eN?Юv9  IVWc#d](bRPNA#RL4*ܴIWn2b>/zPܰ{S;Bc@ϛHlTZ$ *?}D"}@ꜛ`0 %g3fJ*o۷/9͉\nW1Qq\I58>uAxbcoq-Cحs.f1E3hpSoҕ8եbG5m]RAU-oOpERHI )rCqd8^u3@լ-]ҳH%ߞRKGDQuT yn}Tދ6qE;q>ݩ̵<+#%[,d}(T ŸuJuLu 2Ma9;8֙L.bXmDS ^U\xs;u7OTṱ4Hn|oQ^w/@kԉjj69;lA,lGVRjj*IiVM9Y$Xv[ Җspgkq_NS7ݴR8:nn*j&' `#5ZeMRZȡ8=>Iro<TSZQkVBE!c 26=g1ΛVlڑ4&D1@= 7-LGwW5TP(8X $ x\lW{_(@W1@T-@(Bf%dd4-$e$.1c&m`Stf}=o/~ys9߽|DP~ Il h9!34]=1[zZ|VQ!V@s4Q<'aM^J̪J}hӼ-kMk !DIG)b*Ķ焔1^Dȃَ }zbY{O= }!W̠GeoH:f8H{<7Hl>]}1kT8V!PzɆqԧ /Wh4ta q8< `4uɏڧŵvjZv-qƝxkK@%)}5q~Ʒ{v71K ex%+oU:;nVG9>|fe~MQ2nvu = ogx;Û _Z2r9/:~& O3~M 0|/2 0y?W _ck o1:ï37S>s~7fZ3x"D@7-8o~B΍er|'[SVOYvYhC _ $ɜL6gd66xP1i P;ߗsO8ЮP PO=@9cW$5 _,J47BNRO9TaAg> S'ʺLLT(IO2sW?_KņCˈ-tzrŐ!l,1Pf oƐB1-C:B1dk(~3oƐ-CZC1d_(~3 oƐNCŰy`6hܯbRwNw sKo]CĜmq녙W1VrՔ@ hqp2r,};&C:!{CXagʑWr) Z>}#Ta暎9cmkK#P_ǻ?Kmn{[h; Bϧz7ͤ{I6eH }k{J|oH#Q^'ydTG)R.Hױtca^]עYG]^I-:6:XW*ұc:Irzg yuԐ5:QA:[tT8Xb1bhD,Ũtw.sX@Z@@xY.w[o]O_],I,r;.6>DX>,w!w?,NCq}"܅0Bg:]`=O=,w!"":C%E%gx{x?}Y9>"ϔ\sz[-r,oӈwE4gxGK,r95={E=r6;9g 8'kxj{j~bUswJr}gDͤ\卵g6?5@5A4B'C"DKEFG!NO)P)Q%R%S$TU""V""XY)Z([ 1 2+*$W\]_`a+b,c,def'gh$!!i'!j'kl&m%%nop*-J M&L!^qr.s;t@uEv4w8x5y5z5{*|U~./0 !"#02W3U4U5T}T A',)(HI/XR$h9P aD"$7-LGwW5 D 0AA v@8/ʚ;ʚ;g44d4d )0ppp@ <4dddd 0Dt <4BdBdy 0D <4!d!dy 0D0___PPT10 l___PPT9NFP +j ( ?  O  =DPresenter s Disclosure of Interest$#" Sources of Research Support as PI 1. HD049024 (R01) 2. AA07728 (R37) 3. AA13321 (R01) 4. AA11998 (P50) 5. AA07580 (T32) 6. AA015210 (R01) 7. AA09022 (R01) from the National Institute of Child Health and Human Development and the National Institute on Alcohol Abuse and Alcoholism.>"PPP"kGAUSTRALIA: OZ '81VAUSTRALIAN 1981 ( Older ) TWIN COHORT (Heath, Martin, Bucholz, Madden et al.) Recruited from volunteer twin panel Mostly born 1940-1964 (N=5,995 interviews) Spouses also interviewed (N=3,814 interviews); now interviewing the offspring generation. Subsample underwent alcohol challenge testing (N=412) Also used to identify informative sibships for gene-mapping efforts (Madden NAG; Heath/Todd/ Martin/Whitfield Alcohol IRPG). VOZ\ZZ&(],7TlI$AUSTRALIA  OZ '89rAUSTRALIAN 1989 TWIN COHORT (Heath, Martin, Bucholz, Madden, et al.) Born 1964-1971 (N=6,250 interviews) Recruited from volunteer twin panel, enrolled when children Heavy drinking cohort, with high rates of alcohol problems in women as well as men! Just starting to interview the offspring generation. Also used to identify informative sibships for gene-mapping efforts.DE.).,,mJ U.S.A.: VETS KVIETNAM-ERA TWIN PANEL (VETS) (Tsuang, Eisen, True, Jacob, Bucholz, et al.) Identified through military service in the Vietnam Era All male twin panel (N=6712 interviews in Harvard Drug Study) Follow-up assessments of offspring of alcohol dependent and control pairs (Jacob, True) and of drug dependent and control pairs (Bucholz) \L.PnKU.S.A.: MOAFTSMISSOURI ADOLESCENT FEMALE TWIN STUDY (MOAFTS) (Heath, Madden, Bucholz, et al.) Ascertainment from birth records Parent intake interviews with cohorts of twins aged 11, 13, 15, 17, 19 (n=3666 parents, 2190 families) Twin intake interviews at 13, 15, 17, 19 (N=3702 twins, 1799 complete pairs) Continued follow up of twin birth cohort through age 25 (N=3780  including new participants) New NICHD-funded follow up focused on mating, reproducing & parenting.PPz. z? WHY STUDY ALCOHOLISM?( Ideal phenotype for studying the complex interplay of genetic factors, environmental risk mechanisms. Important clinical & public health problem.&h,(WHY EMPHASIZE ALCOHOL PROBLEMS IN WOMEN?0)"Early studies relatively uninformative about genetic influences on risk of alcohol problems in women; Increasing rates of female alcohol use, problems, drinking to intoxication in recent cohorts; Women are usually custodial parents  importance of female alcohol abuse/dependence for GxE interaction? Implications for risk to offspring in next generation?eetWHY AUSTRALIA?: AUSTRALIAN 1989 COHORT ( 90/70 COHORT)$;*90% of men have consumed 9 or more standard drinks in a day 70% of women have consumed 7 or more standard drinks in a day <1% of men, even fewer women, lifetime abstainers:<>$#1oL0HISTORY OF INTOXICATION: AUSTRALIAN FEMALE TWINS11pM=HISTORY OF HEAVY DRINKING (5+ in day) AUSTRALIAN FEMALE TWINS>>rPART ONE (HCRITICAL PERSPECTIVES ON THE BEHAVIORAL GENETIC LITERATURE ON ALCOHOLISMII NA  Medical Genetic model of alcoholismZAssumptions of Strong  Medical Genetic Model..To understand the familial transmission of alcoholism, it is sufficient to understand the underlying GENETIC mechanisms. We can ignore environmental influences as we investigate genes that contribute to risk. REALLY?$Z Z# Genotype x Environment InteractionH The importance of genetic influences may be greatly increased under some environmental conditions, and decreased under others  beyond what would be predicted from the average effects of genetic, environmental risk-factors in the population. = statistical interaction. Same caveats apply.,%u 2 Risk = Genes + Environment + Genes x Environment&s1s3  fIn the beginning & Pioneering Danish Adoption Study CSwedish (Stockholm) Adoption Study - Temperance Board RegistrationsDD 3Stockholm Adoption Study: Unlike-Sex Relative Data44   ' Adoption Study Findings for Alcoholism('Alcohol outcomes in adopted-away offspring (female as well as male) correlate with alcoholism/antisocial personality disorder in biological parents, NOT (usually) with psychopathology of adoptive parents. Suggests intergenerational transmission of alcoholism may be determined by genetic transmission, not environmental transmission. In general, evidence for genotype x environment interaction effects at best equivocal: almost no robust, replicated examples. No significant evidence for genotype x gender interaction  genetic effects equally important in women and men, but sometimes too few women included, given lower base rate of alcohol problems in women, to allow significant effects to be found. "PP Warning !!!In the Stockholm Adoption Study, 32% of biological fathers and 4.7% of biological mothers of adoptees had one or more temperance board registrations. Approximately 14% of Swedish males from the general population had at least one temperance board registration. Fewer than 4% of adoptive families had one or more parents with at least one temperance board registration. i.e., Adoptees tend to come from high-risk genetic backgrounds, are exposed to low risk rearing environments. Not  ideal for GxE analyses. Most of the information from adoption studies is about biological FATHER alcoholism. Nq P PU P Pq,] Example Twin Study: Virginia Twin Study  DSM-IIIR Alcohol Dependence: Female Like-Sex Pairs^^ W Female Like-Sex Twin Correlations for DSM IIIR Alcohol Dependence: Virginia Twin StudyXD /Estimating Parameters of a Simple Genetic Model00 Genetic and Environmental Variance Components: Alcohol Dependence in Women (Virginia Twin Study) (WITH CONFIDENCE INTERVALS!)b  vEstimates of Genetic and Environmental Variances: (Australian 1981 Cohort, N=5995 twins) (DSM-IIIR Alcohol Dependence)ww![ Estimates of Genetic and Environmental Variances: (Australian 1989 Cohort, N=6250 twins) \4( We can elaborate this simple model by jointly modeling (probit) regressions on hypothesized mediating variables of alcoholism risk, estimating residual genetic and environmental effects (and, in principle, G x E interaction effects).s8 +Predictors of Alcoholism Risk (1989 Cohort),,~Gender ! risk in males Education ! risk in early school leavers Religion ! risk with religious involvement Depression ! risk Conduct Disorder ! risk Childhood sexual abuse ! risk (Women only)$"!5Unadjusted versus Adjusted Genetic Variance Estimates66"'Shared Environmental Variance Estimates((#rPHidden Assumption: 1(GUnless environmental moderators are assessed and included in our models,H G"x Contributions of Genetic, Shared Environment, Genotype x Shared Environment Interaction Effects to Twin/Sib Resemblanceyy$_Confounding of GxSE Interaction Applies Equally to Sibling Data with Genetic Marker Information``M 4'Shared Environmental Variance Estimates((8Q Estimates of Genetic and Environmental Variances: (Meta-analysis of U.S. data) R4#6Estimating a Model Allowing for Genetic Non-Additivity77, sOHidden Assumption 2 Strong genetic non-additivity could mask shared environmental influences in the classical twin design, producing zero estimates for shared environmental variance across multiple studies. ASSUMED ABSENT.2f qN 0 We can conduct a sensitivity analysis, fixing different assumed values of the shared environmental variance, and estimating the dominance ratio, i.e. the ratio of non-additive to additive genetic variance, as a free parameter, to determine whether significant shared environmental variance is plausible.21sf 5* Sensitivity Analysis: Alcohol Dependence++sPART TWO ,RECONSIDERING GENE-ENVIRONMENT INTERPLAY IN ALCOHOLISM  A WORK IN PROGRESSLL  XWhat s wrong with the  medical genetic model for alcoholism?? By oversimplifying our model for alcoholism inheritance, it may cause us to overlook complexity, or to infer complexities (e.g., Gene-environment interactions) where none exist. It tempts us to neglect the importance of environmental influences in alcoholism; It may cause us to miss opportunities for gene-discovery (by NOT stratifying on environmental exposure). B?n?{ENVIRONMENTAL INFLUENCES?<GENDER (why have rates of nicotine dependence in men versus women converged, but not rates of alcohol dependence?) COHORT differences PRE-NATAL (& PRE-CONCEPTION) influences EARLY CHILDHOOD TRAUMA (e.g., childhood physical & sexual abuse) OTHER CHILDHOOD ENVIRONMENTAL influences (e.g. parental divorce) Etc etc etc,=ZqSOME SIMPLE QUESTIONS(1) Can genetic factors EVER explain cohort differences in rates of alcoholism? (2) In the general community, do male alcoholics or female alcoholics on average report faster progression from first intoxication to onset of alcohol dependence? (3) & do alcoholics reporting early-onset of alcohol use or alcoholics reporting later onset of alcohol use (e.g. age 13 versus age 18) have faster progression to alcohol dependence? (4) If we match on history of alcohol use (level of consumption), are women more likely to develop alcohol problems or men? (5) Replace gender in (2)-(4) by other hypothesized environmental modifiers of alcoholism risk, e.g. CSA, or psychiatric risk-factors or comorbid conditions (e.g., nicotine dependence).&%HCharacterizing Gene-Environment Interplay: Five Routes to Increased RiskII(Timing of exposure  age at onset of alcohol use; Amount of exposure  quantity consumed; Dependence vulnerability  risk differences, controlling for exposure history; Delayed desistance  persistence in excessive or problem drinking; Psychiatric comorbidity, via (1)  (4)." %&'(& 2Part A: GxE Interaction & Psychiatric Comorbidity33 (!True for depression?<  Major depression is a familial disorder, and its familiality mostly or entirely results from genetic influences . (Sullivan et al., 2000, Am J Psychiatry)VPtiP)Pu)4 `)# Kendler et al, 1993:  Comorbidity between MD (Major Depression) and alcoholism in women is substantial, and appears to result largely from genetic factors that influence the risk to both disorders. 0*"g There Are Good Reasons to Anticipate Important Environment Effects Associated with Parental Alcoholismhhbecause parental alcoholism is a major predictor of high-risk environmental exposures, from conception to young adulthood. high risk exposures are especially likely if biological mother is alcoholic. fetal alcohol and tobacco exposure; family socioeconomic disadvantage, divorce; childhood physical, sexual abuse, other early trauma; parent-parent, parent-child conflict; impaired parental supervision, high-risk peers..PP+$9Intergenerational Influences on Psychiatric Comorbidity??::/&XGenetic and Environmental Contributions to Major Depression Risk: Meta-Analysis Results YY0')Major Depression Risk in Australian Women**3*cSensitivity Analysis: Australian Twin Study, 1989 Cohort (Female like-sex pairs, Major Depression)4d9*4+A More Direct Approach(lCan we identify indices of family environmental risk that are strongly associated with outcomes of interest?,m l5,5 Early Trauma Exposure in MOAFTS and Depression Risk 6-u Association between Maternal Alcoholism (by Parent Report) and Offspring Early Trauma Exposure (by Offspring Report)vv7._ Association between Paternal Alcoholism (by Parent Report) and Offspring Early Trauma Exposure``8/jA More Direct Test: Genetic and Environmental Variance Estimates for Early Trauma Count: European Ancestry"kX90VGenetic and Environmental Variance Estimates for Early Trauma Count: African AmericansWWA1B3> Estimating the Effects of Genotype x Environment Interaction:??C4P Genotype x Environment Interaction in Depression: 1989 Twin Cohort (Cohort 2)Q2D5[ Genotype x Environment Interaction in Depression: Australian 1981 Twin Cohort (Cohort 1),\4'9Danish Adoption StudyVGoodwin, Schulsinger, Knop, Mednick & Guze (1977)  Neither group (adopted away daughters of alcoholics, controls) had higher (than general population) rates of psychopathology, e.g., depression. However, daughters of alcoholics raised by their biological parents had significantly more depression. F22\:Iowa Adoption Studyl Major depression in females was predicted by an alcoholic diathesis only when combined with the disturbed adoptive parent variable. (Cadoret et al, 1996: Am J Psychiat 153:892-9)>1,tUPDATE(High-risk environmental exposures associated with parental alcoholism may be important (inter-generational) contributors to the observed comorbidity of alcohol use and other psychiatric disorders.E2PART B,2 G-E Interplay and the Initiation of Substance Use33$vgGenetic and shared environmental variance estimates for early-onset substance use (by age 14) in MOAFTShhugGenetic and shared environmental variance estimates for early-onset substance use (by age 14) in MOAFTShhF6DOnset of At-Risk Drinking in the Australian Twin Panel (1989 Cohort)Earlier of (a) drinking to intoxication (b) drinking monthly for six months or longer ( regular drinking )llG7<Age-at-Onset Distribution in Australian Women Born 1964-1971==H8:Age-at-Onset Distribution in Australian Men Born 1964-1971;;I9WLifetime Prevalence of Alcohol Dependence in Women, by age-of-onset of at-risk drinkingXXJ:0Lifetime Prevalence of Alcohol Dependence in Men11K;SCrude Association of Alcohol Dependence Rates with Age-at-Onset of At-Risk DrinkingTTM=7Years of At-Risk Drinking as a Function of Age-at-Onset88N>pCumulative incidence of alcohol dependence as function of years of at-risk drinking, stratified by age at onsetqqP@ tQSOME SIMPLE QUESTIONSn(3) & do alcoholics reporting early-onset of alcohol use or alcoholics reporting later onset of alcohol use (e.g. age 13 versus age 18) have faster progression to alcohol dependence?}aB&Heath s Paradox (!)(WAlcoholics who start at-risk drinking earlier have delayed onset of alcohol dependence.XX$bCcDdE?Hazard Ratios as a Function of Age: Onset of Alcohol Dependence@@uRSOME SIMPLE QUESTIONS(2) In the general community, do male alcoholics or female alcoholics on average report faster progression from first alcohol use to onset of alcohol dependence?xvS IT DEPENDS: On the distributions of age at initiation of drinking in women versus men AND the shape of the hazard distributions for onset of alcohol problems in women versus men.*  wLDelay from Onset of Alcohol Use to Onset of Alcohol Dependence: 1989 CohortMM wT JDOES FAMILIAL RISK OF ALCOHOLISM INFLUENCE TIMING OF ONSET OF ALCOHOL USE?KKxUdYES, BUT THROUGH FAMILY NON-INTACTNESS (Note: All analyses of US data-sets control for ethnicity)4e'< yVPercentage of EA families in MOAFTS where family dissolution has occurred, as a function of alcoholism assessed by maternal report vs twin report zW X ZContrast GroupsParental Status Divorced, parental alcoholism Divorced, no parental alcoholism Never married, parental alcoholism Never married, no parental alcoholism Still married, parental alcoholism Still married, no parental alcoholism  comparison group"[bMOAFTS: Hazard Ratios as a function of parental alcoholism and marital status: First alcohol usecc\[MOAFTS: Hazard Ratios as a function of parental age and marital status: First alcohol use\\]"MOAFTS: Age at First Intoxication##^"MOAFTS: Age at First Intoxication##aMOAFTS: Age at First MJ UsedMOAFTS: Age at First SexeUpdate`In the MOAFTS birth cohort (female twins): Parental divorce or never marriage is strongly associated with very early alcohol & illicit drug use This association is especially strong in families with a parental history of alcoholism Parental alcoholism, in intact families, is not an important predictor of very early onset substance use Early (voluntary) sexual behavior shows a similar pattern of association  potential mediator?L+flImpact of divorce and/or parental alcoholism on very early-onset alcohol use: women, NESARC (Hazard Ratios)mmgjImpact of divorce and/or parental alcoholism on very early-onset alcohol use: men, NESARC (Hazard Ratios)kkj  What are potential confounders in relationship between parental marital status and early substance involvement? Severity of parental alcoholism Number of alcoholic parents (1 vs 2) Comorbid anti-social traits (in parents, offspring) History of major depression (in parents, offspring)0q qlpbFinal Model: Very-early Onset Alcohol Use in MOAFTS: Hazard Ratios (and 95% confidence interval)cc q Parenting correlates of early onset alcohol use (controlling for parental alcoholism & family dissolution)mmxPART C,t Should we pay greater attention to differences in dependence vulnerability, i.e., conditioning on drinking history?u%su$yKPercent alcohol dependent by gender, as a function of heaviness-of-drinkingLLzKPercent alcohol dependent by gender, as a function of heaviness-of-drinkingLL{@Percent alcohol dependent by number of alcoholic parents: WOMENAA|>Percent alcohol dependent by number of alcoholic parents: MEN??~@Percent alcohol dependent by history of major depression: WOMENAACPercent alcohol dependent by history of nicotine dependence: WOMENDDFPercent alcohol dependent by history of Childhood Sexual Abuse: WOMENGG@Percent alcohol dependent by history of conduct disorder: WOMENAA@Percent alcohol dependent by history of parental divorce: WOMENAA>Percent alcohol dependent by history of parental divorce: MEN?? And, of course, we should not neglect influences of heaviness of drinking (including genetic factors) And also factors that influence persistence of problems (including genetic?) " x )Major DepressionvPredicts -- increased vulnerability -- earlier onset -- NOT heaviness of drinking -- NOT persistence of problemswwChildhood Sexual AbuseyPredicts -- increased vulnerability -- earlier onset (in women) -- heaviness of drinking -- persistence of problemszzConduct DisorderrPredicts -- earlier onset -- heaviness of drinking -- persistence of problems -- NOT increased vulnerabilityssParental Divorce=Predicts -- earlier onset -- ?? reduced vulnerability (Men)>>Tobacco DependencePredicts -- everything CONCLUSIONS We can consider genes that influence alcohol dependence risk as risk-factors that act jointly with other risk-factors (psychiatric, environmental, etc.) This perspective forces us to ask questions that traditionally have been neglected by psychiatric geneticists about timing of onset of use; level of use; vulnerability conditional on use; Persistence.: " U"  U CONCLUSIONS =Consideration of these different aspects of risk should provide a firmer foundation for dissecting the joint contributions of genetic and environmental factors to alcoholism risk. It may also lead us to adopt new approaches for gene discovery efforts, taking advantage of information about ENVIRONMENTAL risk-factors.>" >, /8 '-:;< = > ? @ RSTUVWXY[\^fghi{!|"}#$&'()*/23458>?@ABCDEFGHIMNOPQRSTUVWXYZ[\]^_`abcdefghijklmnopqrstuvwxyz { | } ~ *+,-./012367;"  ` ` ̙33` 333MMM` ff3333f` f` f` 3>?" dd@ ?" dd<@  " @ ` n?" dd@   @@``PR    @ ` ` p>  >    2*(    6 "N  T Click to edit Master title style! !$  0 "}J  RClick to edit Master text styles Second level Third level Fourth level Fifth level!     S  0 "``  F*0  0 "`   H*0  0L "@  L*"0B  s *޽h ? 33 @Confidentiality and Other IssuesG  (    6rG " G T Click to edit Master title style! !  0PuG "L  G W#Click to edit Master subtitle style$ $Z   # "XhX  Zgֳgֳ ?"   Zgֳgֳ ?" `  s *"Pv  C @A(MED1linepos(CMYK)SM"c{B  s *޽h ? 33 0 p(    NFkk P%   n*  K%%KKpp  Ntkk  %  p*  K%%KKppd  c $ ?(K  4  N.kk  0)  RClick to edit Master text styles Second level Third level Fourth level Fifth level!     S   T]kk P   n*  K%%KKpp   T]kk    p*  K%%KKppH  0޽h ? 3380___PPT10.bI= ((    NT7kk P%  G \* K%%KKpp  N~Gkk  % G ^* K%%KKpp  TČGkk P  G \* K%%KKpp  TGkk   G ^* K%%KKppH  0޽h ? 3380___PPT10.d0l+2 YQ  (   |  0}  Gene-Environment Interplay in Alcoholism (and other substance use disorders): Presentation to Yale CTNA April 24, 2006 Do Not Copy Slides Without Permission From Dr. Heath T0H dN)5-  0Ȕ Z2 }Andrew C. Heath, D.Phil. Midwest Alcoholism Research Center Department of Psychiatry Washington University School of Medicine4~0 eH  0޽h ? a(y___PPT10Y+D=' = @B +J  qi0((  (x ( c $`   x ( c $    ( 0 EName & Presentation Date: Andrew C. Heath, D.Phil., April 24, 2006 6F0 2)j ( 0 C  Consulting Relationships -- Palo Alto VA (Jacob) Stock Equity (> $10,000) -- NONE Speaker s Bureau(s) -- NONE 5 4 5  4 4 5  4 5   XB ( 0D0H ( 0޽h ? fy___PPT10Y+D=' = @B +@ yq@0(  0 0 < ԫPx|L t"Genetic Epidemiology of Alcoholism6#0 "$( 0 0h٫,c  1Understanding, in the general population, the complex interplay of genetic and environmental risk-factors in determining (a) differences in alcoholism risk, (b) the comorbidity of alcoholism with other disorders, and (c) differences in the course of alcohol problems and associated outcomes through time..20 1 &$hhB 0 s *޽h ? a( A P6(  ~  s *۫N   x  c $׫  H  0޽h ? 33___PPT10i.1 {{+D=' = @B +E B \T`(  ~  s *N     c $   0c   fgֳgֳ ?"@ 0 H  0޽h ? 33___PPT10i.1 {{+D=' = @B + C ph(  ~  s *<N      0 S" cc  H  0޽h ? 33___PPT10i.1 {{+D=' = @B +A D XP(  ~  s *N     c $     fgֳgֳ ?" 0H  0޽h ? 33___PPT10i.1 {{+D=' = @B + E H0(  Hx H c $t#<<   x H c $$  H H 0޽h ? 33___PPT10i.1(.b+D=' = @B +3 F JBh(  hx h c $L*~   ~ h s *+J   h  fgֳgֳ ?"P @@H h 0޽h ? 33___PPT10i.1`&+D=' = @B + G 0(  x  c $j   x  c $k&  H  0޽h ? 33___PPT10i.1` ͆+D=' = @B +9& H P%H%00$(  ~  s *t7e   ~#  # #":. <"   # lD3gֳgֳ ?"  V  @`  # lDDgֳgֳ ?" n   L16.3 @`  # lNgֳgֳ ?"n  PPre 1916   @`  # l`Tgֳgֳ ?" 2 n  L25.8 @`  # l\gֳgֳ ?"2 n  O1916-23 @`   # l\cgֳgֳ ?"  2  L25.3 @`   # l lgֳgֳ ?" 2  O1924-31 @`   # lsgֳgֳ ?"    L46.9 @`   # lugֳgֳ ?"   O1932-39 @`   # l$gֳgֳ ?"   L52.8 @`  # l@gֳgֳ ?"   O1940-47 @`  # l쒭gֳgֳ ?"  L70.1 @`  # lDgֳgֳ ?"  O1948-55 @`  # l0gֳgֳ ?"  L78.5 @`  # lLgֳgֳ ?"  O1956-64 @`  # l쳭gֳgֳ ?"  \87.5& @`  # l|gֳgֳ ?"  O1964-71 @`  # lpgֳgֳ ?"  V % Ever Drunk   @`   fƭgֳgֳ ?"  W Year of Birth @`B  Tgֳgֳo?" B  Zgֳgֳo?"B  Tgֳgֳo?"B  Tgֳgֳo?"B  Zgֳgֳo?" B  Zgֳgֳo?" B  Tgֳgֳ1 ?"  B  Tgֳgֳo?"B  Tgֳgֳo?" B   Tgֳgֳo?"B ! Tgֳgֳo?"B " Tgֳgֳo?"B # Tgֳgֳo?" B $ Tgֳgֳo?"  B % Tgֳgֳo?" 2 B & Tgֳgֳo?"2 n B ' Tgֳgֳo?"n  B ( Tgֳgֳo?"B ) Tgֳgֳo?"B * Tgֳgֳo?" B + Tgֳgֳo?"  B , Tgֳgֳo?" 2 B - Tgֳgֳo?"2 n B . Tgֳgֳo?"n  B / Tgֳgֳ1 ?"  0  fgֳgֳ ?"H  0޽h ? 33___PPT10i.1+D=' = @B +%& I <%4%01$(  ~  s *حY   j# b 1 #":. <"b   # lgֳgֳ ?" V  @`  # lgֳgֳ ?"  L 7.8 @`  # lgֳgֳ ?"  PPre 1916   @`  # lgֳgֳ ?" r   L22.0 @`  # lgֳgֳ ?"r  O1916-23 @`   # l gֳgֳ ?" _ r  L20.1 @`   # lgֳgֳ ?"_ r  O1924-31 @`   # l4gֳgֳ ?" N _  L41.4 @`   # lH"gֳgֳ ?"N _  O1932-39 @`   # l)gֳgֳ ?" ; N  L50.4 @`  # l1gֳgֳ ?"; N  O1940-47 @`  # l@:gֳgֳ ?" (;  L65.9 @`  # l\<gֳgֳ ?"( ;  O1948-55 @`  # lHJgֳgֳ ?" .( L77.4 @`  # ldLgֳgֳ ?". ( O1956-64 @`  # l[gֳgֳ ?" . \83.5& @`  # lUgֳgֳ ?" . O1964-71 @`   # legֳgֳ ?" b Z% Heavy Drinking @`  Thm ?"b  W Year of Birth @`B  Tgֳgֳo?"b bB  Zgֳgֳo?"B  Tgֳgֳo?"bB  Tgֳgֳo?"bB  Zgֳgֳo?"B  Zgֳgֳo?"B  Tgֳgֳ1 ?"B  Tgֳgֳo?".B  Tgֳgֳo?" bbB   Tgֳgֳo?".B ! Tgֳgֳo?".(B " Tgֳgֳo?"(; B # Tgֳgֳo?"; N B $ Tgֳgֳo?"N _ B % Tgֳgֳo?"_ r B & Tgֳgֳo?"r  B ' Tgֳgֳo?" B ( Tgֳgֳo?".(B ) Tgֳgֳo?"(; B * Tgֳgֳo?"; N B + Tgֳgֳo?"N _ B , Tgֳgֳo?"_ r B - Tgֳgֳo?"r  B . Tgֳgֳo?" B / Tgֳgֳ1 ?"  0  fgֳgֳ ?"@H  0޽h ? 33___PPT10i.1+D=' = @B +$ M $(  r  S    r  S X0   H  0޽h ? 3380___PPT10.cPV! N Dg(  D:B D 3 oEW  D <t C  P UNAFFECTED* 0  :B D 3 o>a  D < ;2/  P UNAFFECTED* 0  :B D 3 o a  D  `X1?&]  La) Threshold model0  D  `1?  Ub) Multiple-threshold model0   D BTC1 DEFo..1 a Z  ' _ ) jvlLUp5Nw{) 6 , > M , ` >   w) Iq  ;tm F,  L  I - T1 ]`@s W   D <D  C  NAFFECTED* 0 @B  D@ C o  @B  D C o  @B  D@ C o  @B D C o  x  D <|'   >MILD0   D <,   ?CASES0  @B D@ C o S $ @B D C o & FB D@ S o   D <'   @SEVERE0   D < 9  ?CASES0  FB D@ S o q  D BC1 DEFo,,1 a Z  ' _ ) jvlLUp5Nx{) 6 - A G 9 p   x <D   Rz~V G-  v  + Y\@c kW vB D NDo?$ h $ vB D NDo?$ H $  D  `1?7  IAlcoholism Risk0  D  `1?7 t IAlcoholism Risk0 x D c $Ķw   B D s *޽h ? a(  0(  x  c $X@   x  c $躱  H  0޽h ? 33___PPT10i.1(.b+D=' = @B + O lZ(  l~ l s *LN    l s *± x  * 1QYH l 0޽h ? fy___PPT10Y+D=' = @B +$ P  t$(  tr t S رN   r t S ر  H t 0޽h ? 3380___PPT10.b*W%  %$0--L$(  L~ L s *8߱N     L 0H h  \At least in males, risk of alcoholism appeared to be genetically transmitted within families ] -2] BB L 6  O(Goodwin et al, 1973)0"r `@i  L# #"2i@`i  L # lD ?" si  T  @` L # l  ?"0s  T   @` L # l  ?"@s0 R  @`  L # l  ?" i  L4% @`  L # l ?"s i  L5% @`  L # l ?" i  L3% @`  L # l  ?" i  M17% @`  L # l( ?" i  L2% @` L # l0 ?" i  M18% @` L  f9 ?"` i  [Lifetime Alcoholism @`  L # l@ ?"0  ZDaughters [N=47]  @` L # lB ?"s0  U Sons [N=78]    @` L # lQ ?" 0  fNon-Adopted Daughters [N=81]  @` L # lS ?" 0  aNon-Adopted Sons [N=20]  @` L # la ?"0  gAdopted-Away Daughters [N=49]  @` L # l,\ ?"0  bAdopted-Away Sons [N=55]  @` L  fq ?"`0  R   @`  L # lhs ?"s@0 YControl Parents @`  L # lT{ ?"@0 [Alcoholic Parents @` L  f  ?"`@0 R   @`B L Zgֳgֳo?"`@@B L Zgֳgֳo?"`@`0B L Zgֳgֳo?"@0B L Tgֳgֳo ?"i i B L Tgֳgֳo ?" i i B L Tgֳgֳo ?"si i B  L Zgֳgֳo?"` `i B !L Zgֳgֳo?"`0` B "L Zgֳgֳo?"@@B #L Zgֳgֳo?"@s@B $L Zgֳgֳo?"s@@B %L Zgֳgֳo?"0 B &L Zgֳgֳo?" i B 'L Tgֳgֳ1 ?"00B (L Tgֳgֳ1 ?"s00B )L Zgֳgֳo?"`i i B *L Zgֳgֳo?"i i B +L Zgֳgֳo?" i i B ,L Zgֳgֳo?"i si B -L Zgֳgֳo?"i i H L 0޽h ? ̙33y___PPT10Y+D=' = @B +& Q &&@00T&(  T~ T s *l\<    T  `3gֳgֳ ?"p'! I ,0(2 T 6 B(Cloninger et al, 1981, 1988, and reanalyzed in Heath et al, 1997)C0C 9`#z /  T# #"&  T T| ?"S   T  @` T T ?" S   L27 @` T T ?" S  L20 @`  T T ?"S   M125 @`  T TIJ ?"S   Q Recurrent   @`  T T@Ͳ ?" S  T  @`  T T|ϲ ?" S  K9 @`  T T,ײ ?" S  K5 @` T T߲ ?"  S  L82 @` T T ?" S  KOne @`  T T4 ?"  o 0.19 0.062 " @` T TX ?"   L51 @` T T ?"   L39 @` T T4  ?"  M504 @` T T ?"  LNone @`  T  fgֳgֳ ?") aTetrachoric correlation @` T  f!gֳgֳ ?" ) S Recurrent   @` T  fL/gֳgֳ ?" )  MOne @` T  f7gֳgֳ ?")  NNone @` T  f?gֳgֳ ?") YBiological Father @` T  fFgֳgֳ ?"/) P  @` T  fHgֳgֳ ?"/) YAdopted-Away Sons @` T  fHVgֳgֳ ?"/) P  @`B T Zgֳgֳo?"//B T Zgֳgֳo?"  B T Zgֳgֳo?"/)B  T Zgֳgֳo?"/)B !T Zgֳgֳo?"//B "T Zgֳgֳo?")B #T Zgֳgֳo?"//B $T Zgֳgֳo?")B %T Zgֳgֳo?" B &T Zgֳgֳo?" B 'T Zgֳgֳo?" S B (T Zgֳgֳo?" S B )T Zgֳgֳo?"S B *T Zgֳgֳo?"S  B +T Zgֳgֳo?"  B ,T Zgֳgֳo?" B -T Zgֳgֳo?"  B .T Zgֳgֳo?"  B /T Tgֳgֳ1 ?"B 0T Tgֳgֳ1 ?"))H T 0޽h ? ̙331 R ~1v1P@`d1(  dx d c $j     d  `gֳgֳ ?"h'! ZTemperance Board Registrations 0(2p +  `d #""i+  d T` ?" # +  K9 @` d TG ?" # +  L23 @` d Tw ?"# +  S One or more   @`  d T ?" #  M142 @`  d T ?"  #  M688 @`  d Tl ?" #  LNone @` d  flgֳgֳ ?"  U One or more   @` d  f<gֳgֳ ?"   NNone @` d  flgֳgֳ ?"  YBiological Mother @` d  fXgֳgֳ ?"  [Adopted-Away Sons @` d  fgֳgֳ ?"  R  @`B d Zgֳgֳo?" B d Zgֳgֳo?"+ + B d Zgֳgֳo?"B d Zgֳgֳo?"B d Zgֳgֳo?" B d Zgֳgֳo?"B d Zgֳgֳo?"B d Zgֳgֳo?"# B d Zgֳgֳo?"# B d Zgֳgֳo?"# + B d Zgֳgֳo?"# + B  d Zgֳgֳo?" + + B !d Zgֳgֳo?" + + B #d Tgֳgֳ1 ?" B $d Tgֳgֳ1 ?" p ` Id #"") ` &d TǴ ?"0 T  @` 'd T д ?"0 T  @` (d T״ ?"g0 T  @` )d Tߴ ?"0g R  @` *d TL ?"]0 V  @` +d T ?"]0 T  @` ,d T ?"g]0 T  @` -d Tt ?"]g0 R  @` .d  f|gֳgֳ ?"] T  @` /d  fgֳgֳ ?"] T  @` 0d  fgֳgֳ ?"g] T  @` 1d  f4gֳgֳ ?"g] R  @` 2d  f%gֳgֳ ?"` P  @` 3d  f`-gֳgֳ ?"g` R  @` 4d  f4gֳgֳ ?"`g P  @`B 5d Zgֳgֳo?"`g`B 6d Zgֳgֳo?"gB 7d Zgֳgֳo?"`B 8d Zgֳgֳo?"`B 9d Zgֳgֳo?"g``B :d Zgֳgֳo?"]B ;d Zgֳgֳo?"``B d Zgֳgֳo?"]0B ?d Zgֳgֳo?"0B @d Zgֳgֳo?"0B Ad Zgֳgֳo?"gB Bd Zgֳgֳo?"B Cd Zgֳgֳo?"B Dd Tgֳgֳ1 ?"]g]B Ed Tgֳgֳ1 ?"g ]d 69   e%Tetrachoric correlation = 0.17 0.11$&4 <&H d 0޽h ? ̙33S sk`X(  X X s *   |LGenetic and Environmental Variance Estimates in the Stockholm Adoption StudyMML X  `,ȴgֳgֳ ?"% t Additive Genetic 95% Confidence Variance Interval % Pooled: 37 19-56u0 2ur X  `gֳgֳ ?#" ` h NOTE: No significant association of adoptee and adoptive parent temperance board registration(s), suggesting family environment effects unimportant.0 2 X 6LS   MSignificance of genotype x gender interaction: X2 = 1.51, d.f. = 3, p = 0.68.8N0 20 H X 0޽h ? ̙33 T p\~(  \~ \ s *ZI    \ s *찧   , \ 3 r_gֳgֳ ?"0 * |@Danish; Swedish (Bohman, Cloninger, Sigvardsson); Iowa (Cadoret) A0AH \ 0޽h ? 33y___PPT10Y+D=' = @B + U `<(  `~ ` s *gN   ~ ` s *hW  H ` 0޽h ? ̙33F  mex(  x~ x s *<WP0    x 6  & Lifetime Risk to cotwin of an Recurrence Risk N Prevalencea (%) alcohol-dependent twin (%) Ratio MZ pairs 590 8.1 31.6 3.9 DZ pairs 440 10.2 24.4 2.4Rf0 P500P>[4]  x 6$^  O(Kendler et al, 1992)0 x 6% O  Fa Proportion of individuals reporting a history of alcohol dependence.&G0FH x 0޽h ? ̙33y___PPT10Y+D=' = @B + V  y(  ~  s *L0   r O  # #"GonO    fgֳgֳ ?" O  T  @`   fĕgֳgֳ ?" r  T  @`  # lHgֳgֳ ?" r T  @`    fgֳgֳ ?" O  `0.12  0.56   @`   fgֳgֳ ?" O  N0.35 @`    fTgֳgֳ ?" O  KDZF @`     fǵgֳgֳ ?"r  `0.34  0.69   @`    fTϵgֳgֳ ?"r  N0.53 @`    fеgֳgֳ ?"r  KMZF @`   # lصgֳgֳ ?"r a95% Confidence Interval @`  # lgֳgֳ ?" r aTetrachoric Correlation @`   fPgֳgֳ ?"r R  @`B  Zgֳgֳo?"B  Zgֳgֳo?"O O B  Zgֳgֳo?"rB  Zgֳgֳo?"rB  Zgֳgֳo?" B  Zgֳgֳo?"r B  Zgֳgֳo?" B  Zgֳgֳo?"B  Zgֳgֳo?"r B  Zgֳgֳo?" O B  Zgֳgֳo?" O B  Zgֳgֳo?"O O B  Zgֳgֳo?" O O B  Zgֳgֳo?"O O B  Tgֳgֳ1 ?"r rB  Tgֳgֳ1 ?"rr  6p^ [!(Kendler et al, 1992, reanalyzed)"0"H  0޽h ? ̙33y___PPT10Y+D=' = @B +J W aY (  ~  s *r   3  h # #"fvh    fgֳgֳ ?#" `  y VG is (additive) genetic variance; VSE is shared environmental variance; VNSE is non-shared environmental variance.Xz $ & ' @`   fgֳgֳ ?#" `h  U where    @`  # l"gֳgֳ ?"   @VG + VSE VG + VSE 1  VG  VSE!       @`  # lgֳgֳ ?"  O= = = @`l  # l6gֳgֳ ?"h   rMZ rDZ VNSEP    $ @`B   Zgֳgֳo?"hB   Zgֳgֳo?"hB   Zgֳgֳo?"hh B   Zgֳgֳo?" B   Zgֳgֳo?" B  Zgֳgֳo?"h hB  Zgֳgֳo?" B  Zgֳgֳo?" B  Zgֳgֳo?"H  0޽h ? 33___PPT10i.%P+D=' = @B +Q X $$(  ~  s *Bj    v Qt  # #""`onnQt    fIgֳgֳ ?" t  O31-66 @`   fJgֳgֳ ?"   T  @`   fPgֳgֳ ?"0    L47 @`   fXgֳgֳ ?" 0  g!Non-shared environmental variance"" @`   f_gֳgֳ ?"   T  @`    fmgֳgֳ ?"=  T  @`   # logֳgֳ ?"Q= T  @`    fxgֳgֳ ?" t  N0-55 @`    fgֳgֳ ?"0   L17 @`    fDgֳgֳ ?" 0   cShared environmental variance @`   fДgֳgֳ ?"=t  N0-69 @`   fPgֳgֳ ?"0 =  L36 @`    fgֳgֳ ?"=0  _Additive genetic variance @`  # lgֳgֳ ?"Qt= a95% Confidence Interval @`  # lgֳgֳ ?"0 Q= K% @`   fgֳgֳ ?"Q0 = R  @`B  Zgֳgֳo?"Q0 QB  Zgֳgֳo?" 0 B  Zgֳgֳo?"Q=B  Zgֳgֳo?"tQt=B  Zgֳgֳo?"0 QQB  Zgֳgֳo?"= B  Zgֳgֳo?"QQB  Zgֳgֳo?"QtQB  Zgֳgֳo?"t=t B  Zgֳgֳo?" B  Zgֳgֳo?"t t B  Zgֳgֳo?"0  B   Zgֳgֳo?"  B ! Zgֳgֳo?" t B " Tgֳgֳ1 ?"0 ==B # Tgֳgֳ1 ?"=t= $ 6E  [!(Kendler et al, 1992, reanalyzed)"0"H  0޽h ? ̙33 Y  (    TlͶ1?G   95% Variance (%) Confidence Interval Additive Genetic 64 32 - 73 Shared Environment 1 0 - 27 Non-Shared Environment 35 27 - 47F0 %0 \0   ~  s *϶R   V   fٶgֳgֳ ?" P `NOTE: No genotype x gender interaction: X2 = 0.38, d.f. = 1, p = 0.54 (Heath et al., 1997). 6a0* 6B  s *޽h ? a(y___PPT10Y+D=' = @B + Z m(  ~  s *P     T1?   95% Variance (%) Confidence Interval Additive Genetic 53 32 - 61 Shared Environment 0 0 - 16 Non-Shared Environment 47 39 - 55F0 %0 \0     3 rpgֳgֳ ?"n XDSM-IV Alcohol Dependence"0   fgֳgֳ ?"p  lNOTE: No genotype x gender interaction (X2 = 1.61, d.f=3, p=0.66) (Knopik et al., 2004) Controlling for sociodemographic variables and prior psychiatric history reduces heritability minimally. N0+ mEz<@@H  0޽h ? ̙33y___PPT10Y+D=' = @B +2  2(  r  S N     S  }J  H  0޽h ? 3380___PPT10.d    zr (  r  S N     S 4   &   0< P  l(Knopik et al, 2004)(2H  0޽h ? 3380___PPT10.d   (    0"py > Unadjusted (95% CI) Adjusted (95% CI) 53% 33-61% 47% 28-55%? 2?} *r  S %M   H  0޽h ? 3380___PPT10.dD   (    0|0y 6 Unadjusted (95% CI) Adjusted (95% CI) 0 0-15 0 0-147 27} *x  c $2M   H  0޽h ? 3380___PPT10.dD ~v0(    0= v" BEWARE: SIMPLIFYING ASSUMPTIONS!!#(2# } *H  0޽h ? 3380___PPT10.dD \ @j(  x  c $Fof     c $hL@    0@  0P iP  TConfounding of genetic effects and genotype x shared environment interaction effects6U  <T@H  0޽h ? 33___PPT10i..+D=' = @B + [ Pe(  ~  s *\] P0]   l p   #"888p   T8c ?"   S 1 x =    @`  Tl ?"   K @`  T0s ?"  K1 @`  Tx| ?"   ZDZ Pairs/Full Sibs @`  Tp~ ?"  S 1 x 1 = 1   @`   T ?"   K1 @`   Tԓ ?"  K1 @`   T ?"  PMZ Pairs   @`    T ?"p q)Genotype x Shared Environment Interaction** @`   T ?" p `Additive Genetic Effects @`  T賸 ?"p  \Shared Environment @`  T< ?"p P  @`B  Zgֳgֳo?"  B  Zgֳgֳo?"pB  Zgֳgֳo?"pB  Tgֳgֳ1?"p pB  Zgֳgֳo?"ppB  Zgֳgֳo?" ppB  Zgֳgֳo?" B  Zgֳgֳo?"ppB  Zgֳgֳo?" B  Zgֳgֳo?" B  Zgֳgֳo?"  B  Zgֳgֳo?" B  Zgֳgֳo?"  B  Zgֳgֳo?"     `gֳgֳ ?" _S B0 2 H  0޽h ? fy___PPT10Y+D=' = @B +~ ] `$$5(  ~  s *0Ǹ   [v   # #""   # l<и ?"0   S 1 x 0 = 0   @`  # lhظ ?"  0  K0 @`  # l ?"  K1 @`  # lp ?"   K0 @`  # l ?"0/   S 1 x =    @`   # lp ?" / 0  K @`   # lx ?"/   K1 @`   # l8  ?"/   K1 @`   # l ?"0P/  S 1 x 1 = 1   @`   # lL ?" P0/  K1 @`  # l! ?"P /  K1 @`  # lT) ?"P/  K2 @`(  # l1 ?"0P v,Trait locus x shared environment interaction-- @`  # ld3 ?" 0P cTrait locus (QTL) effects @`  # lxA ?" P \Shared environment @`  # lpC ?"P l"Identity by descent at trait locus## @`B  Zo?"B  Zo?"  B  Zo?"PB  Zo?"PB  Zo?" B  Zo?"P/ B  Zo?" 0B  Zo?"0B  Zo?"P/ B  Zo?"/  B  Zo?"/  B  Zo?" B   Zo?"  B ! Zo?" B " Zo?" 0 B # Zo?"0   $  `DOgֳgֳ ?" V vi.e. GxSE can be very helpful  if we can identify the environmental conditions under which genetic effects are especially strongly amplified. 0H  0޽h ? fy___PPT10Y+D=' = @B +  p(    0y 6 Unadjusted (95% CI) Adjusted (95% CI) 0 0-15 0 0-147 27} *x  c $XWM   H  0޽h ? 3380___PPT10.dDU  |t (  ~  s *Te     Tf1?ip  D 95% Variance (%) Confidence Interval Additive Genetic 58 43 - 67 Shared Environment 2 0  16F0 %0 90 e  *  3 rtkgֳgֳ ?" z< Alcoholism variously defined"0L   fvgֳgֳ ?" P: DNOTE: No genotype x gender interaction (X2 = 0.49, d.f=3, p=0.92) 6E0+  `H  0޽h ? ̙33y___PPT10Y+D=' = @B +G ^ ^V (  ~  s *xr   0  h1 # #"t3h1    fgֳgֳ ?#" `Q 1 2VG is additive genetic variance; VNAG is non-additive (dominance or epistatic) genetic variance; VSE is shared environmental variance.X   = #D : @`   fgֳgֳ ?#" `h Q R where    @`  # lgֳgֳ ?"1  $VG + VNAG + VSE VG + VNAG + VSE%       @`  # lgֳgֳ ?"  M= = @`[  # lgֳgֳ ?"h  rMZ rDZD  $ @`B   Zgֳgֳo?"hB   Zgֳgֳo?"hQB   Zgֳgֳo?"hh B   Zgֳgֳo?"11 B   Zgֳgֳo?"B  Zgֳgֳo?"h hB  Zgֳgֳo?"1B  Zgֳgֳo?"1 1B  Zgֳgֳo?"Q1H  0޽h ? 33___PPT10i.%P+D=' = @B + _ 0(  x  c $ù   x  c $`Ĺ05  H  0޽h ? 33___PPT10i..+D=' = @B + ` &(  ~  s *}J  H  0޽h ? 33___PPT10i.:z4+D=' = @B +  (M(  ~  s * ϹP0   p p`P ( #""8888x  ' T|ٹ ?"p `P U 31% (8-38%)   @` & TL۹ ?" pP T 3% (2-23%)   @` % T ?" P M20% @`  Tt ?"p `  U 29% (3-43%)   @`  T ?" p  U 10% (3-34%)   @`  T ?"   M15% @`  T  ?"p`  U 23% (0-46%)   @`   T  ?"p  U 21% (0-45%)   @`   T ?"  M10% @`   T,# ?"pp` gNon-additive Genetic Variance @`   T+ ?"pp cAdditive Genetic Variance @`   T, ?"p o%Assumed Shared Environmental Variance&& @`B  Zgֳgֳo?"pB  Zgֳgֳo?"`p`B  Tgֳgֳ1?"ppB  Zgֳgֳo?"pppB  Zgֳgֳo?" B  Zgֳgֳo?"pp`pB  Zgֳgֳo?"`` B  Zgֳgֳo?" PB  Zgֳgֳo?"` `PB  Zgֳgֳo?"PPB  Zgֳgֳo?"PpPB  Zgֳgֳo?"pP`P   `8gֳgֳ ?" _S B0 2 H  0޽h ? fy___PPT10Y+D=' = @B +$ a $(  r  S @   r  S 4,P,0   H  0޽h ? 3380___PPT10.ca0  |0(  |x | c $GN   x | c $H}J  H | 0޽h ? 3380___PPT10.b@K>0  0(  x  c $MN   x  c $HN}0J  H  0޽h ? 3380___PPT10.br^F  F(  x  c $DU-     c $\0  "8GCH  0޽h ? 3380___PPT10.b`N  N(  x  c $\lN     c $,t   *H  0޽h ? 3380___PPT10.bBP,& Z&R& /V%(  %   V #":. "lfffRfffZ    # l ?"<6  ` (F)$ @`   # l} ?"6< XCSA/early trauma @`   # l4 ?"< 6 R  @`    # l ?" <6 ZFamily dissolution @`   # lࡺ ?"<j  X$ @`   # l ?"j <  ZTobacco dependence @`  # lt ?"< j  ` (F)$ @`  # l人 ?" <j  VPanic disorder @`   # lº ?"<   X$ @`   # l˺ ?"<  XMajor depression @`   # lͺ ?"<L  Z$ @`    # l\ܺ ?"L< XConduct disorder @`  $ # l ?"< L X$ @` % # l\ ?"<L VFamily history @` ) # lp ?"<  N @` * # l ?"< T Birth cohort   @`& . # l ?"<  tVariable (md"f)& " @` / # l ?"< NGender @` 3 # l ?"<  \Timing of onset @` 4  f ?"< R  @`B 5 Zgֳgֳo?"<B 6 Zgֳgֳo?"<B 7 Zgֳgֳo?"B 8 Zgֳgֳo?"  B 9 Zgֳgֳo?"< B : Zgֳgֳo?"B > Zgֳgֳo?"  B ? Zgֳgֳo?"B @ Zgֳgֳo?"  B A Zgֳgֳo?"LB B Zgֳgֳo?"  LB C Zgֳgֳo?"LB D Zgֳgֳo?" L B E Zgֳgֳo?" B F Zgֳgֳo?"   B G Zgֳgֳo?" j B H Zgֳgֳo?"  j B I Zgֳgֳo?"j B J Zgֳgֳo?" j B K Zgֳgֳo?" 6B L Zgֳgֳo?" 6B M Zgֳgֳo?"6B N Zgֳgֳo?" 6 B O Zgֳgֳo?"< B S Tgֳgֳ1 ?"< H  0޽h ? 3380___PPT10.c3 220;T2(  1   T #":. "lfffRfffZ    # l: ?#" ` 6  X$ @`  # l,5 ?"<6  ` (F)$ @`   # lH ?"6< XCSA/early trauma @`   # lP ?#" ` 6 Y---$ @`    # llY ?"< 6 X$ @`    # l$a ?" <6 ZFamily dissolution @`  # lc ?#" ` j  P @`   # l,r ?"<j  X$ @`   # l@z ?"j <  ZTobacco dependence @`  # l ?#" `  j  Y---$ @`  # l} ?"< j  ` (F)$ @`  # l  ?" <j  VPanic disorder @`  # l ?#" `    Y---$ @`   # l\ ?"<   X$ @`   # l ?"<  XMajor depression @`  # l ?#" ` L  Z$ @`   # l찻 ?"<L  Z$ @`    # l<ǻ ?"L< XConduct disorder @` # # l(ɻ ?#" `  L P @`  $ # lѻ ?"< L X$ @` % # l߻ ?"<L VFamily history @` ( # l ?#" `   N @` ) # l ?"<  N @` * # l ?"< T Birth cohort   @` - # lX ?"   l (M>f)*  @`& . # l  ?"<  tVariable (md"f)& " @` / # l ?"< NGender @` 2 # l$ ?"   ^Level of consumption @` 3 # l# ?"<  \Timing of onset @` 4  fT+ ?"< R  @`B 5 Zgֳgֳo?"<B 6 Zgֳgֳo?"<B 7 Zgֳgֳo?"B 8 Zgֳgֳo?"  B 9 Zgֳgֳo?"< B : Zgֳgֳo?"B ; Zgֳgֳo?"  B > Zgֳgֳo?"  B ? Zgֳgֳo?"B @ Zgֳgֳo?"  B A Zgֳgֳo?"LB B Zgֳgֳo?"  LB C Zgֳgֳo?"LB D Zgֳgֳo?" L B E Zgֳgֳo?" B F Zgֳgֳo?"   B G Zgֳgֳo?" j B H Zgֳgֳo?"  j B I Zgֳgֳo?"j B J Zgֳgֳo?" j B K Zgֳgֳo?" 6B L Zgֳgֳo?" 6B M Zgֳgֳo?"6B N Zgֳgֳo?" 6 B O Zgֳgֳo?"< B P Zgֳgֳo?"  B S Tgֳgֳ1 ?"< H  0޽h ? 3380___PPT10.cc? >>@GTc>(  +> ( T #":. "lfffRfffZ(   # ldD ?#" ` 6( X$ @`  # lxM ?#" ` 6  X$ @`  # lpV ?"<6  ` (F)$ @`   # lQ ?"6< XCSA/early trauma @`   # lg ?#" ` (6 f?? (M$)& @`   # lp ?#" ` 6 Y---$ @`    # lj ?"< 6 X$ @`    # l ?" <6 ZFamily dissolution @`  # lЉ ?#" ` j (  X$ @`  # l ?#" ` j  P @`   # l ?"<j  X$ @`   # l ?"j <  ZTobacco dependence @`  # l ?#" `  (j  Y---$ @`  # l ?#" `  j  Y---$ @`  # l ?"< j  ` (F)$ @`  # l Ž ?" <j  VPanic disorder @`  # l ǽ ?#" ` (  X$ @`  # l\ս ?#" `    Y---$ @`   # l޽ ?"<   X$ @`   # lP ?"<  XMajor depression @`  # ld ?#" ` L( Y---$ @`  # l ?#" ` L  Z$ @`   # lX ?"<L  Z$ @`    # l  ?"L< XConduct disorder @` " # l( ?#" ` (L \()$ @` # # l ?#" `  L P @`  $ # l# ?"< L X$ @` % # l& ?"<L VFamily history @` ' # l`3 ?#" ` ( M? @` ( # l< ?#" `   N @` ) # l|C ?"<  N @` * # lL ?"< T Birth cohort   @`( , # lU ?" ( v (F>m)6 @` - # lhP ?"   l (M>f)*  @`& . # lg ?"<  tVariable (md"f)& " @` / # la ?"< NGender @`  1 # lq ?" ( W Vulnerability @` 2 # l ?"   ^Level of consumption @` 3 # l聾 ?"<  \Timing of onset @` 4  f( ?"< R  @`B 5 Zgֳgֳo?"<B 6 Zgֳgֳo?"<B 7 Zgֳgֳo?"B 8 Zgֳgֳo?"((B 9 Zgֳgֳo?"< B : Zgֳgֳo?"B ; Zgֳgֳo?"  B < Zgֳgֳo?" (B > Zgֳgֳo?"((B ? Zgֳgֳo?"B @ Zgֳgֳo?"((B A Zgֳgֳo?"LB B Zgֳgֳo?"((LB C Zgֳgֳo?"LB D Zgֳgֳo?"(L(B E Zgֳgֳo?" B F Zgֳgֳo?"(( B G Zgֳgֳo?" j B H Zgֳgֳo?"( (j B I Zgֳgֳo?"j B J Zgֳgֳo?"(j ( B K Zgֳgֳo?" 6B L Zgֳgֳo?"( (6B M Zgֳgֳo?"6B N Zgֳgֳo?"(6(B O Zgֳgֳo?"< B P Zgֳgֳo?"  B Q Zgֳgֳo?" (B S Tgֳgֳ1 ?"<(H  0޽h ? 3380___PPT10.cK &KKPSSJ(  ~J N # #":. "lfffRfffZ   # l߽ ?#" `P  X$ @`  # ld ?#" ` P X$ @`  # l\ ?#" `  X$ @`  # lľ ?"I  ` (F)$ @`   # l4Ǿ ?" I XCSA/early trauma @`  # lTԾ ?#" `P>   Y---$ @`   # l0 ?#" `> P  f?? (M$)& @`   # lؾ ?#" ` >   Y---$ @`    # l ?"I>  X$ @`    # l ?"> I  ZFamily dissolution @`   # l ?#" `P >  X$ @`  # l ?#" ` P>  X$ @`  # l ?#" ` >  P @`   # l ?"I >  X$ @`   # lX! ?" I>  ZTobacco dependence @`  # l() ?#" `Pr   Y---$ @`  # l$ ?#" `r P  Y---$ @`  # l: ?#" ` r   Y---$ @`  # lhC ?"Ir  ` (F)$ @`  # lHK ?"r I  VPanic disorder @`  # lM ?#" `P r  Y---$ @`  # lLO ?#" ` Pr  X$ @`  # le ?#" ` r  Y---$ @`   # ln ?"I  r  X$ @`   # lu ?" Ir  XMajor depression @`  # lXx ?#" `P  X$ @`  # ly ?#" `P  Y---$ @`  # lL ?#" `   Z$ @`   # l ?"I  Z$ @`    # l ?"I  XConduct disorder @`N ! # l ?#" `PT  (2 alc. Par.)$ @` " # lH ?#" `TP \()$ @` # # l ?#" ` T P @`  $ # l`ÿ ?"IT  X$ @` % # l˿ ?"TI VFamily history @` & # lͿ ?#" `PT M? @` ' # lտ ?#" `PT M? @` ( # l ?#" ` T N @` ) # l ?"I T N @` * # l8 ?"IT T Birth cohort   @` + # l ?"P N @`( , # l ?"P v (F>m)6 @` - # l  ?"  l (M>f)*  @`& . # l0 ?"I  tVariable (md"f)& " @` / # l ?"I NGender @` 0 # l( ?"PN U Persistence   @`  1 # l0 ?"NP W Vulnerability @` 2 # l8 ?" N ^Level of consumption @` 3 # l@ ?"IN  \Timing of onset @` 4  fH ?"NI R  @`B 5 Zgֳgֳo?"NINB 6 Zgֳgֳo?"IB 7 Zgֳgֳo?"NB 8 Zgֳgֳo?"NB 9 Zgֳgֳo?"IN NB : Zgֳgֳo?"B ; Zgֳgֳo?" NNB < Zgֳgֳo?"NPNB = Zgֳgֳo?"PNNB > Zgֳgֳo?"B ? Zgֳgֳo?"TB @ Zgֳgֳo?"TB A Zgֳgֳo?"TB B Zgֳgֳo?"TB C Zgֳgֳo?" B D Zgֳgֳo?" B E Zgֳgֳo?" r B F Zgֳgֳo?" r B G Zgֳgֳo?"r B H Zgֳgֳo?"r  B I Zgֳgֳo?" > B J Zgֳgֳo?" > B K Zgֳgֳo?"> B L Zgֳgֳo?">  B M Zgֳgֳo?" B N Zgֳgֳo?" B O Zgֳgֳo?"I B P Zgֳgֳo?" B Q Zgֳgֳo?"PB R Zgֳgֳo?"PB S Tgֳgֳ1 ?"IH  0޽h ? 3380___PPT10.cv b `v(  r  S cN      6Ac"$ `   H  0޽h ? 3380___PPT10.b G c p<(  ~  s *P0T   ~  s *   H  0޽h ? 33___PPT10i.,Х+D=' = @B +  J(  ~  s *rN     s *DyBB0   fH  0޽h ? ̙33y___PPT10Y+D=' = @B + d <(  ~  s *́P0M   ~  s *  H  0޽h ? f  e  x(  x  c $x      ` gֳgֳ ?" D0(2    `<gֳgֳ ?";w OPARENTAL ALCOHOLISM 0(2   ` gֳgֳ ?"d h g+OFFSPRING HIGH-RISK ENVIRONMENTAL EXPOSURES ,0(2,   `̕gֳgֳ ?"K  `$OFFSPRING GENETIC RISK OF DEPRESSION %0(2%   `Tgֳgֳ ?"  U  POFFSPRING DEPRESSION 0(2B   `gֳgֳD?"i9 B  @  `gֳgֳD?"^ Y B   `gֳgֳD?"[    `gֳgֳ ?" g `&(Simplified from Heath & Nelson, 2002)'0(2'H  0޽h ? 33___PPT10i.40)}+D=' = @B +  ?7(  x  c $yY}   |  6( cWB   % 95% Confidence Interval Genetic Variance 37 31-42 Shared Environmental Variance 0 0-5 Non-Shared Environmental Variance 63 58-67N0i0i_ bB2z  0QF q D0 2   6 =  '(Sullivan et al., 2000, Am J. Psychiat)(0(H  0޽h ? ̙33y___PPT10Y+D=' = @B +  v(  x  c $TD     6 5Z  % 95% CI % 95% CI Genetic Variance 44 29-53 35 13-44 Shared Environmental Variance 0 0-12 0 0-17 Non-Shared Environmental Variance 56 47-65 65 56-74 (Bierut, et al., 1999, Arch Gen Psychiatry; Heath, et al., unpublished)B0H0HA&  bB2z  6Ob8o YAustralian Adult Twin Surveys 0  6@ G  1981 Cohort 1989 CohortH0  $H  0޽h ? ̙33y___PPT10Y+D=' = @B +1* f H)@)11((  ~  s *l   ( c} # #"."+c}    fgֳgֳ ?" P95% CI @`   fgֳgֳ ?"  M% @`   fxgֳgֳ ?"7  R  @`   fgֳgֳ ?"7 R  @`   f8gֳgֳ ?"Nu } P  @`s    f gֳgֳ ?"u N} }i.e. CONSISTENT WITH 5-10% CONTRIBUTION OF SHARED FAMILY ENVIRONMENT TO RISK OF MAJOR DEPRESSION, MASKED BY GENETIC DOMINANCE~~ @`    fgֳgֳ ?"u } R  @`    fgֳgֳ ?" u  L1-26 @`    fgֳgֳ ?" u  M 2 @`    f$gֳgֳ ?"7 u  O >7.0 @`   f2gֳgֳ ?" 7u  M20% @`   f4gֳgֳ ?"   L2-32 @`   fAgֳgֳ ?"   M 5 @`   f\Igֳgֳ ?"7  P 4.1 @`   fKgֳgֳ ?" 7  M15% @`   flYgֳgֳ ?"   L2-38 @`   fagֳgֳ ?"   L20 @`   fcgֳgֳ ?"7  P 0.5 @`   fjgֳgֳ ?" 7  M10% @`   fhlgֳgֳ ?"  L3-44 @`   fygֳgֳ ?"   L34 @`   fgֳgֳ ?"7  K0 @`   fgֳgֳ ?"7  N 5% @`!  T` ?" c = ESTIMATED ADDITIVE GENETIC VARIANCE>> @`  TԚ ?"7c  {1 ESTIMATED DOMINANCE RATIO22 @`   T ?"c7 o%ASSUMED FAMILY ENVIRONMENTAL VARIANCE&& @`B  Zgֳgֳo?"c7cB  Zgֳgֳo?"cB   Zgֳgֳo?"cB ! Zgֳgֳo?"7c cB " Zgֳgֳo?"B # Zgֳgֳo?" ccB $ Zgֳgֳo?"B % Zgֳgֳo?" B & Zgֳgֳo?" B ' Zgֳgֳo?"  B ( Zgֳgֳo?"  B ) Zgֳgֳo?" }B * Zgֳgֳo?" }B + Zgֳgֳ1 ?"}N}B , Zgֳgֳ1 ?"u }B - Zgֳgֳ1 ?"Nu N}B . Tgֳgֳ1 ?"  B / Zgֳgֳ1 ?"u Nu B 0 Zgֳgֳo?"}}B 1 Zgֳgֳo?"N}}H  0޽h ? 33___PPT10i.`q,+D=' = @B + g D(  x  c $,of     c $0#X   0@H  0޽h ? 33___PPT10i..+D=' = @B +a*   * *34)(  ~  s *\       f|gֳgֳ ?" |>NCS traumatic events experienced by age 13 (European Ancestry)"?0?% d' 4 #"2&     d'   f} ?"H  d' X  @`   ` ?" H ' S 3210 @`   f ?" ' X  @`   fX ?"H d  S 90.0 @`    ` ?" H   a 11 " @`     fD ?"   ^ 5 or more @`    f  ?"H d  S 50.0 @`    ` ?" H  Q 20 @`    fl  ?"   S4h@`   f8 ?"H d  S 58.3 @`   `x ?" H  Q 48 @`   f" ?"   S3h@`   f* ?"H d  S 47.4 @`   `2 ?"H  R 135 @`   f; ?"  S2h@`   f(C ?"H d S 26.3 @`   `hK ?"H  R 555 @`   fxS ?" S1h@`   f[ ?"H d S 15.8 @`   `c ?"H  S 2441 @`   fl ?" M0h@`   fs ?"H d pMajor Depression History %$  @`   `4 ?"H  MN @`    f ?" ^Events experienced @`B  To?"B  To?"B  To?"ddB   T1?"'H 'B ! To?"H B " To?"B # To?"H dB $ To?"ddB % To?"B & To?"ddB ' To?" B ( To?"dd B ) To?"  B * To?"d d B + To?"  B , To?"d d B - To?" 'B . To?"d d'B / T1 ?"dB 0 Zo?"''B 1 Zo?"H 'd'B 2 ZgֳgֳD?", l k - 4 3  `gֳgֳ ?" @Polyserial correlation with depression = 0.37 (95% CI 0.31-0.42) A0(2A 7H  0޽h ? ̙33#'   &&-4c&(  ~  s *ؠA   <   `ugֳgֳ ?"d\d $21=35.27, p<.0001^0(2"**" #| b  4 #".",m())')b    fdx ?"9 b  P25.0 @`N   f8Y ?"9 b F>6___PPT9 T27.8  @`   f ?"9 b  N4+ @`   fx ?" 9  P10.0 @`M    fY ?" 9 F>6___PPT9 S8.8  @`    f ?" 9  M3 @`    f@x ?"   P11.1 @`M    fY ?"  F>6___PPT9 S5.7  @`    f< ?"   M2 @`   fx ?"  O5.2 @`M   fY ?" F>6___PPT9 S8.9  @`   f$  ?"  M1 @`   fx ?" O2.9 @`M   f0Y ?"F>6___PPT9 S3.3  @`   f ?" M0 @`    f) ?" aAfrican American % @`    f2 ?" aEuropean Ancestry % @`   # l4: ?" Z Trauma Count   @`    f B ?" aMaternal Alcoholism @`   fI ?" V  @`B  Zo?"B  Zo?"b b B  Zo?"B  Zo?"B  Zo?"B  Zo?"B  Zo?"B   Zo?"B ! Zo?"B " Zo?" B # Zo?" B $ Zo?"  B % Zo?"  B & Zo?" 9 B ' Zo?" 9 B ( Zo?"9 b B ) Zo?"9 b B * Zo?"b b B + Zo?"b b B , Tgֳgֳ1 ?"< -  `Pgֳgֳ ?"dxd $21=17.41, p<.0001^0(2"**" H  0޽h ? ̙33)'   &&-3i&(  ~  s *t A   <   `TRgֳgֳ ?"d\d $21=23.19, p<.0001^0(2"**" )#| b  3 #".",m())')b    flj  ?"9 b  P25.0 @`N   fl _ ?"9 b F>6___PPT9 T33.4  @`   fy ?"9 b  N4+ @`   f|  ?" 9  P20.0 @`N    fD _ ?" 9 F>6___PPT9 T38.2  @`    f  ?" 9  M3 @`    f8  ?"   P18.5 @`N    f$ _ ?"  F>6___PPT9 T30.5  @`    fL ?"   M2 @`   f  ?"  P14.3 @`N   f _ ?" F>6___PPT9 T24.6  @`   f ?"  M1 @`   fh  ?" P17.3 @`N   f _ ?"F>6___PPT9 T18.4  @`   f ?" M0 @`    f ?" aAfrican American % @`   fT ?" gEuropean Ancestry %@ @`   # lx ?" Z Trauma Count   @`    f ?" aPaternal Alcoholism @`   f ?" V  @`B  Zo?"B  Zo?"b b B  Zo?"B  Zo?"B  Zo?"B  Zo?"B  Zo?"B   Zo?"B ! Zo?"B " Zo?" B # Zo?" B $ Zo?"  B % Zo?"  B & Zo?" 9 B ' Zo?" 9 B ( Zo?"9 b B ) Zo?"9 b B * Zo?"b b B + Zo?"b b B , Tgֳgֳ1 ?"6 -  `L gֳgֳ ?"dxd 21=0.07, p>0.9^0(2"** " H  0޽h ? ̙33)    "&i(  ~  s *h      `@zgֳgֳ ?"T$ Z0 2 ,&p   & #""ooo    fH'gֳgֳ ?" ^   Y27-41"%(2 @`   fD!gֳgֳ ?", ^  [ 33 % 2  @`8   f0gֳgֳ ?"^ ,  Non-Shared Env. Variance % 2   @`   f$@gֳgֳ ?" ^  Y34-68"%(2 @`    fL;gֳgֳ ?",  ^  [ 54 % 2  @`4    fIgֳgֳ ?", ^  Shared Env. Variance % 2  @`    fXgֳgֳ ?"  X0-36"%(2 @`    f`Tgֳgֳ ?",   m 13NS0% 2  @`    f`jgֳgֳ ?",  bGenetic Variance % 2 @`   frgֳgֳ ?"  k95% Confidence Interval"%(2 @`   f`zgֳgֳ ?",   V % % 2 @`   fgֳgֳ ?",  R  @`B  Zgֳgֳo?", B  Zgֳgֳo?" , B  Zgֳgֳo?"B  Tgֳgֳ1 ?"^ B  Zgֳgֳo?"B  Zgֳgֳo?"  B  Zgֳgֳo?", B  Tgֳgֳ1 ?", ^ ^ B  Zgֳgֳo?"^ B  Tgֳgֳ1 ?", B  Zgֳgֳo?"^ B  Zgֳgֳo?"B  Tgֳgֳ1 ?", , ^ B  Zgֳgֳo?",  B   Zgֳgֳo?" B ! Zgֳgֳo?"B  Zgֳgֳo?"^  } "  `gֳgֳ ?"` ` i.e., we appear to be indexing environmental risk (but have not yet completely excluded possibility of confounding with genetic risk in parents).20 2 fH  0޽h ? ̙33   YQ0!! (   ~   s *L       `gֳgֳ ?"T Z0 2 ,+v h    # #""oooh      fgֳgֳ ?" &   Y26-53"%(2 @`    fgֳgֳ ?", &  [ 39 % 2  @`8    fXgֳgֳ ?"& ,  Non-Shared Env. Variance % 2   @`    fDgֳgֳ ?"  &  Y34-73"%(2 @`    f,gֳgֳ ?",  &  [ 61 % 2  @`4    fgֳgֳ ?", &  Shared Env. Variance % 2  @`    fgֳgֳ ?" H  X0-31"%(2 @`    f<gֳgֳ ?", H  l 0NS0% 2  @`    fgֳgֳ ?"H,  bGenetic Variance % 2 @`    fgֳgֳ ?" h H k95% Confidence Interval"%(2 @`    fgֳgֳ ?", h H V % % 2 @`    f$gֳgֳ ?"h, H R  @`B   Zgֳgֳo?"h, hB   Zgֳgֳo?" , B   Zgֳgֳo?"hHB   Tgֳgֳo ?"  & B   Zgֳgֳo?" h HB   Zgֳgֳo?" &  B   Zgֳgֳo?"  B   Zgֳgֳo?", B   Tgֳgֳ1 ?", & & B   Zgֳgֳo?"& B   Tgֳgֳ1 ?",  B   Zgֳgֳo?"& B   Zgֳgֳo?"HB   Tgֳgֳ1 ?", , & B   Zgֳgֳo?", h hB   Zgֳgֳo?" h hB !  Zgֳgֳo?" H H   0޽h ? ̙33h @p(  2  BjJ3  u9Genetic Risk-Factors for Alcohol Dependence (in parents) :0: 2  B`jJ c l0Genetic Risk Factors for Depression (in parents) 101   BpjJH @ WParental Alcohol Dependence 0   B(jJx @ OParental Depression 0 XB  0DoXB  0DoXB @ 0Do x    03  @??"0(2    BjJ$   h,High-Risk Environmental Exposure of Children -0-    BD"jJ< C >  ZInteractive Effect of Genetic Vulnerability to Depression High-Risk Environmental Exposure [0[    B&jJ 0N  u9Genetic Risk-Factors for Alcohol Dependence (in children) :0:    B*jJ X  \ Alcohol Dependence (in children) !0!   B4!jJ;   TDepression (in children) 0 XB @ 0DogX; g  6P1o  @??"0(2 XB  0DopXB @ 0DoU XB  0Do@ RB  s *Do C < RB @ s *Do < XB  0DjJN XB @ 0Do [2  <\63jJ[  n2Genetic Risk-Factors for Depression (in children) 303 H  0޽h ? fy___PPT10Y+D=' = @B +  ogP(  ~  s *\<3p    r @  # #"a   ZDgֳgֳ ?"   K ?? @`  ZtMgֳgֳ ?"   |,High Risk Environment - Parental Alcoholism- @`  ZDOgֳgֳ ?"  K ?? @`   Z(Vgֳgֳ ?"  0Low Risk Environment - No Parental Alcoholism1 @`  Z|Xgֳgֳ ?"@ V Heritability   @`   Z`gֳgֳ ?"@ R  @`B   Tgֳgֳo?"@@B   Tgֳgֳo?"  B   Tgֳgֳo?"@B   Tgֳgֳo?"@B  Tgֳgֳo?"@@B  Tgֳgֳo?" B  Tgֳgֳo?" B  Tgֳgֳo?"  B  Tgֳgֳo?"  B  Tgֳgֳo?"     f4pgֳgֳ ?" T~( Note: We control simultaneously for the overall regression of offspring risk on parental alcoholism (to control for GE correlation effects associated with parental alcoholism). 0H  0޽h ? 3  ME`$(  $~ $ s *vN   r P  $# #"PP  $ HN ?"b@  O23-37 @` $ HH ?" @b  L21 @` $ H ?"@  ^No Parental Alcoholism @` $ H\ ?"b   O25-63 @` $ Hܙ ?" b  L49 @`  $ HС ?"   [Parental Alcoholism @`  $ H ?"bP@ a95% Confidence Interval @`  $ Z\gֳgֳ ?" Pb@ a Heritability"  @`  $ Zgֳgֳ ?"P @ R  @`B  $ Tgֳgֳo?"P PB $ Tgֳgֳo?"  B $ Tgֳgֳo?"P@B $ Tgֳgֳo?"P@B $ Tgֳgֳo?" PbPB $ Tgֳgֳo?"@ B $ Tgֳgֳo?"bPPB $ Tgֳgֳo?"@ B $ Tgֳgֳo?"  B $ Tgֳgֳo?"  B $ Tgֳgֳo?"  b B $ Tgֳgֳo?"b  H $ 0޽h ? 3 i ;3p ,(  ,~ , s *4q   r   ,# #"PPP  , # lP ?", 0  T  @` , # l ?",T0  T  @` , # l ?",0T T  @` , # l ?"0   O26-72 @` , # lh ?" ,  L56 @`   , # l ?"  [Parental Alcoholism @`  , # l ?"0T  N6-43 @`  , # lD ?" T,  L30 @`  , # lX ?"T  ^No Parental Alcoholism @`  , # l ?"0T a95% Confidence Interval @`  , # l ?" ,T ZGenetic Variance @` ,  fL- ?" T R  @`B , Zgֳgֳo?" B , Zgֳgֳo?" B , Zgֳgֳo?"TB , Zgֳgֳo?"TB , Zgֳgֳo?" ,B , Zgֳgֳo?"T B , Zgֳgֳo?",0B , Zgֳgֳo?"0B , Zgֳgֳo?"T B , Zgֳgֳo?" B , Zgֳgֳo?"  B , Zgֳgֳo?" , B , Zgֳgֳo?", 0 B , Zgֳgֳo?"0  B , Tgֳgֳ1 ?" T,TB , Tgֳgֳ1 ?"0TT  ,  f2gֳgֳ jJ?" @ JA Replication! 0(2H , 0޽h ? f   J(  ~  s *N     s *B}J  fH  0޽h ? ̙33  $D(  $~ $ s *GN    $ c $x   H $ 0޽h ? 33$ j $(  r  S RN   r  S dS}J  H  0޽h ? 3380___PPT10.c0 k 0(  x  c $tY    x  c $0Z0   H  0޽h ? 3380___PPT10.b G5 r  5(  x  c $_gM   }    #"."GFGEDE  b  # l`gֳgֳ ?"> F>6___PPT9 b38((" x""_7   # lgֳgֳ ?" >  WEarly-onset sex @`b  # logֳgֳ ?"> G  F>6___PPT9 b46((" x""_7   # l8wgֳgֳ ?"G >  U Marijuana use @`b   # lgֳgֳ ?">  G F>6___PPT9 b38((" x""_7   # lXgֳgֳ ?" > G  `Drinking to intoxication @`b  # lgֳgֳ ?">  F>6___PPT9 b42((" x""_7   # lLgֳgֳ ?" >   WAny alcohol use @`b  # lgֳgֳ ?"> u F>6___PPT9 b14((" x""_7  # lgֳgֳ ?"u>  VRegular smoker @`b  # l\gֳgֳ ?"> .uF>6___PPT9 b46((" x""_7   # lؾgֳgֳ ?".> u YAny cigarette use @`{  # lgֳgֳ ?"> .F>6___PPT9 {Additive Genetic Variance*(" x&&_7  # lgֳgֳ ?"> . R  @`B  Tgֳgֳ?"B  Tgֳgֳ?"B  Tgֳgֳ?"B  Tgֳgֳ?"H  0޽h ? 3380___PPT10.bP bT  q %T(  x  c $gM      % #"."GFGEDE  f  # lgֳgֳ ?" F>6___PPT9 f34((" ""Z2 zRb  # lgֳgֳ ?" F>6___PPT9 b38((" x""_7   # lgֳgֳ ?"   WEarly-onset sex @`f  # lTgֳgֳ ?"w  F>6___PPT9 f31((" ""Z2 zRb  # lgֳgֳ ?"w  F>6___PPT9 b46((" x""_7  # lgֳgֳ ?" w   U Marijuana use @`f  # lgֳgֳ ?"2 w F>6___PPT9 f28((" ""Z2 zRb  # ltgֳgֳ ?"2 w F>6___PPT9 b38((" x""_7  # lgֳgֳ ?" 2 w  `Drinking to intoxication @`f  # l$ gֳgֳ ?" 2 F>6___PPT9 f28((" ""Z2 zRb  # l gֳgֳ ?" 2 F>6___PPT9 b42((" x""_7    # l\7gֳgֳ ?"  2  WAny alcohol use @`f   # l)gֳgֳ ?" F>6___PPT9 f63((" ""Z2 zRb   # lHGgֳgֳ ?" F>6___PPT9 b14((" x""_7   # lpIgֳgֳ ?"   VRegular smoker @`f   # l`Qgֳgֳ ?"^F>6___PPT9 f31((" ""Z2 zRb  # l_gֳgֳ ?"^F>6___PPT9 b46((" x""_7   # lagֳgֳ ?" ^ YAny cigarette use @`  # l0jgֳgֳ ?"^F>6___PPT9 Shared Environmental Variance*(" EEZ2 zR{  # lrgֳgֳ ?"^F>6___PPT9 {Additive Genetic Variance*(" x&&_7  # lgֳgֳ ?" ^ R  @`B  Tgֳgֳ?" B  Tgֳgֳ?" B  Tgֳgֳ?"  B  Tgֳgֳ?"H  0޽h ? 3380___PPT10.bP bN  0N(  0x 0 c $HJ    0 c $@0  *irJ " H 0 0޽h ? 3380___PPT10.b l/  f/^/'(8.(  8x 8 c $؏N   >.  (8 #">2 ss S 8  fgֳgֳ ?"< F>6___PPT9 Y100.08(" &R 8  f(gֳgֳ ?"` < F>6___PPT9 X32068(" &Q 8  f4gֳgֳ ?"` F>6___PPT9 WTOTAL6 " &Z 8 # lgֳgֳ ?"< F>6___PPT9 Z13.8:(" &Y 8 # lhgֳgֳ ?"` < F>6___PPT9 Y442:(" &]  8 # lgֳgֳ ?" ` F>6___PPT9 ] 20 or older6 "  &W  8 # llgֳgֳ ?"<  F>6___PPT9 W6.58(" &W  8 # lgֳgֳ ?"` < F>6___PPT9 W2088(" &T  8 # lgֳgֳ ?" ` F>6___PPT9 T196 " &X  8 # lgֳgֳ ?"<  F>6___PPT9 X27.28(" &W 8 # lDgֳgֳ ?"` < F>6___PPT9 W8728(" &T 8 # l(gֳgֳ ?" ` F>6___PPT9 T186 " &X 8 # lgֳgֳ ?"< C  F>6___PPT9 X20.08(" &W 8 # lgֳgֳ ?"` C < F>6___PPT9 W6408(" &T 8 # l\gֳgֳ ?"C ` F>6___PPT9 T176 " &X 8 # lgֳgֳ ?"< C F>6___PPT9 X16.88(" &W 8 # lgֳgֳ ?"` < C F>6___PPT9 W5398(" &T 8 # lgֳgֳ ?"` C F>6___PPT9 T166 " &W 8 # llgֳgֳ ?"< F>6___PPT9 W8.88(" &W 8 # lgֳgֳ ?"` < F>6___PPT9 W2818(" &T 8 # lgֳgֳ ?"` F>6___PPT9 T156 " &W 8 # lgֳgֳ ?"< F>6___PPT9 W3.98(" &W 8 # lpgֳgֳ ?"` < F>6___PPT9 W1248(" &W 8 # l(gֳgֳ ?"` F>6___PPT9 WAt 146 " &W 8 # lgֳgֳ ?"< F>6___PPT9 W3.18(" &W 8 # lgֳgֳ ?"` < F>6___PPT9 W1008(" &W 8 # lgֳgֳ ?"` F>6___PPT9 WBy 136 " &Y 8 # l$gֳgֳ ?"< sF>6___PPT9 Y%<(" &Y  8 # lgֳgֳ ?"` s< F>6___PPT9 YN<(" & !8 # lgֳgֳ ?"s`  R  @`k "8 # lgֳgֳ ?"` sF>6___PPT9 kOnset of At-Risk Drinking6 " & #8 # lgֳgֳ ?"` s R  @`B $8 Ngֳgֳ?"B %8 Ngֳgֳ?"B &8 Ngֳgֳ?"B '8 Ngֳgֳ?"H 8 0޽h ? 3380___PPT10.b:p(  '''(@p'(  @x @ c $8N   & k (@ #">2 ssk  @  fgֳgֳ ?"< k 9100.0 @  fجgֳgֳ ?"` < k 82701Q @  f gֳgֳ ?"` kF>6___PPT9 WTOTAL6 " & @ # l\2gֳgֳ ?"<  96.4 @ # l\5gֳgֳ ?"` <  9174]  @ # lP8gֳgֳ ?" ` F>6___PPT9 ] 20 or older6 "  &  @ # lP=gֳgֳ ?"< u   73.9  @ # l@gֳgֳ ?"` u <  7106T  @ # l(Agֳgֳ ?"u ` F>6___PPT9 T196 " &  @ # lCgֳgֳ ?"< U u  821.1 @ # l Hgֳgֳ ?"` U < u  7569T @ # lJgֳgֳ ?"U ` u F>6___PPT9 T186 " & @ # lMgֳgֳ ?"< 5 U  819.8 @ # lQgֳgֳ ?"` 5 < U  7535T @ # lxTgֳgֳ ?"5 ` U F>6___PPT9 T176 " & @ # lYgֳgֳ ?"<  5  821.6 @ # l[gֳgֳ ?"`  < 5  7582T @ # l^gֳgֳ ?" ` 5 F>6___PPT9 T166 " & @ # l\agֳgֳ ?"<   813.5 @ # legֳgֳ ?"` <   7364T @ # l,fgֳgֳ ?"`  F>6___PPT9 T156 " & @ # l$kgֳgֳ ?"<  76.8 @ # lPogֳgֳ ?"` <  7184W @ # lrgֳgֳ ?"` F>6___PPT9 WAt 146 " & @ # l sgֳgֳ ?"<  76.9 @ # lxgֳgֳ ?"` <  7187W @ # l{gֳgֳ ?"` F>6___PPT9 WBy 136 " &u @ # l|gֳgֳ ?"< sF>6___PPT9 u%: " &Z2 zRs  @ # ldgֳgֳ ?"` s< F>6___PPT9 sN: " &x_7 !@ # lėgֳgֳ ?"s`  R  @`k "@ # llgֳgֳ ?"` sF>6___PPT9 kOnset of At-Risk Drinking6 " & #@ # lgֳgֳ ?"` s R  @`B $@ Ngֳgֳ?"B %@ Ngֳgֳ?"kkB &@ Ngֳgֳ?"kB '@ Ngֳgֳ?"kH @ 0޽h ? 3380___PPT10.b:`%  $$$$H`$(  Hx H c $@N   # p   H# #":. ;  H # l@gֳgֳ ?"0  @  H # lgֳgֳ ?" 0 74.8] H # lgֳgֳ ?"p F>6___PPT9 ] 20 or older6 "  & H # lgֳgֳ ?"0  >  H # l|gֳgֳ ?" 0 77.7T  H # ltgֳgֳ ?"p F>6___PPT9 T196 " &  H # l|gֳgֳ ?"0{  >   H # l0gֳgֳ ?" { 0 813.5T  H # lgֳgֳ ?"p{ F>6___PPT9 T186 " &  H # lxgֳgֳ ?"0[ {  >  H # lgֳgֳ ?" [ 0{  815.2T H # lgֳgֳ ?"p[ { F>6___PPT9 T176 " & H # lgֳgֳ ?"0; [  >  H # lgֳgֳ ?" ; 0[  821.7T H # lgֳgֳ ?"p; [ F>6___PPT9 T166 " & H # lpgֳgֳ ?"0 ;  >  H # lgֳgֳ ?"  0;  831.3T H # lgֳgֳ ?"p ; F>6___PPT9 T156 " & H # lgֳgֳ ?"0   >  H # lgֳgֳ ?" 0  829.8W H # llgֳgֳ ?"p  F>6___PPT9 WAt 146 " & H # lgֳgֳ ?"0  >  H # lxgֳgֳ ?" 0 843.0W H # lLgֳgֳ ?"p F>6___PPT9 WBy 136 " &n H # lgֳgֳ ?"0[ F>6___PPT9 n*("  Z2 zRu H # lgֳgֳ ?" [0F>6___PPT9 u%<(" &x_7 H # lgֳgֳ ?"p[  NONSET: @`\ H # lgֳgֳ ?"  [F>6___PPT9 \ Prevalence6 "  &  H # l"gֳgֳ ?"p  [ R  @`B !H Ngֳgֳ?"p   B "H Ngֳgֳ?"p B #H Ngֳgֳ?"p pB $H Ngֳgֳ?"   H H 0޽h ? 3380___PPT10.b:b%  $$ $$Pb$(  Px P c $$N   # p   P# #":. ;  P # l5gֳgֳ ?"0  @  P # lp8gֳgֳ ?" 0 810.3] P # l;gֳgֳ ?"p F>6___PPT9 ] 20 or older6 "  & P # lgֳgֳ ?"0  >  P # l|@gֳgֳ ?" 0 814.2T  P # lAgֳgֳ ?"p F>6___PPT9 T196 " &  P # lFgֳgֳ ?"0{  >   P # lPIgֳgֳ ?" { 0 821.8T  P # lgֳgֳ ?"p{ F>6___PPT9 T186 " &  P # lDgֳgֳ ?"0[ {  >  P # lQgֳgֳ ?" [ 0{  829.4T P # l Ugֳgֳ ?"p[ { F>6___PPT9 T176 " & P # lYgֳgֳ ?"0; [  >  P # lx\gֳgֳ ?" ; 0[  834.4T P # lx_gֳgֳ ?"p; [ F>6___PPT9 T166 " & P # l0cgֳgֳ ?"0 ;  >  P # legֳgֳ ?"  0;  843.1T P # l6___PPT9 T156 " & P # llgֳgֳ ?"0   >  P # logֳgֳ ?" 0  855.4W P # ltrgֳgֳ ?"p  F>6___PPT9 WAt 146 " & P # lxsgֳgֳ ?"0  >  P # lygֳgֳ ?" 0 845.5W P # l|gֳgֳ ?"p F>6___PPT9 WBy 136 " &n P # lT}gֳgֳ ?"0[ F>6___PPT9 n*("  Z2 zRu P # lĎgֳgֳ ?" [0F>6___PPT9 u%<(" &x_7 P # lHgֳgֳ ?"p[  NONSET: @`\ P # lȘgֳgֳ ?"  [F>6___PPT9 \ Prevalence6 "  &  P # lHgֳgֳ ?"p  [ R  @`B !P Ngֳgֳ?"p   B "P Ngֳgֳ?"p B #P Ngֳgֳ?"p pB $P Ngֳgֳ?"   H P 0޽h ? 3380___PPT10.b:)  ) )0##X((  Xx X c $(N   &  X# #"6* 6/-.-.-.- v X # l[gֳgֳ ?"; F>6___PPT9 v0.2  0.5( ("  ""Z2 zRh X # lظgֳgֳ ?" ;F>6___PPT9 h 0.3& " |""_7 X # lgֳgֳ ?"  S 20 or older   @`v X # l4gֳgֳ ?";  F>6___PPT9 v0.4  0.8( ("  ""Z2 zRh X # lgֳgֳ ?" ; F>6___PPT9 h 0.6& " |""_7  X # lgֳgֳ ?"  J19 @`f  X # ldgֳgֳ ?";_  F>6___PPT9 f--((" ""Z2 zRi  X # lgֳgֳ ?" _ ; F>6___PPT9 i 1.00& " |""_7  X # lgֳgֳ ?"_  J18 @`v  X # lgֳgֳ ?";1 _ F>6___PPT9 v1.1  1.6( ("  ""Z2 zRh X # lgֳgֳ ?" 1 ;_ F>6___PPT9 h 1.3& " |""_7 X # lgֳgֳ ?"1 _  J17 @`v X # l@gֳgֳ ?"; 1 F>6___PPT9 v1.5  2.2( ("  ""Z2 zRh X # lxgֳgֳ ?"  ;1 F>6___PPT9 h 1.8& " |""_7 X # l'gֳgֳ ?" 1  J16 @`v X # l/gֳgֳ ?"; F>6___PPT9 v2.2  3.5( ("  ""Z2 zRh X # lH8gֳgֳ ?" ; F>6___PPT9 h 2.8& " |""_7 X # l@gֳgֳ ?"   J15 @`v X # lHgֳgֳ ?";F>6___PPT9 v2.5  4.5( ("  ""Z2 zRh X # lTBgֳgֳ ?" ;F>6___PPT9 h 3.6& " |""_7 X # lp_gֳgֳ ?"  MAt 14 @`v X # l`gֳgֳ ?";zF>6___PPT9 v2.5  4.5( ("  ""Z2 zRi X # ljgֳgֳ ?" z;F>6___PPT9 i 3.4#& " |""_7 X # lXxgֳgֳ ?"z  Q By age 13   @` X # lygֳgֳ ?";zF>6___PPT9 95% Confidence IntervalL(" &&""Z2 zR X # lgֳgֳ ?" ;zF>6___PPT9  Odds RatioJ " &&x_7 X # lpgֳgֳ ?" z R  @`B X Ngֳgֳ?"B  X Ngֳgֳ?"B !X Ngֳgֳ?"B "X Ngֳgֳ?"  #X  `gֳgֳ ?"`PZ n4# Women: OR = 5.2 (3.3-8.1); Men: OR = 2.6 (1.9-3.7)50 25H X 0޽h ? 3380___PPT10.b:\  @h\(  hx h c $ĢN    }  h# #"&vtvsp@  l h # lgֳgֳ ?"t  F>6___PPT9 l 7.7& "  ""Z2 zRh h # lgֳgֳ ?"7 t  F>6___PPT9 h 8.0& " |""_7 h # lgֳgֳ ?"t 7  S 20 or older   @`m h # lgֳgֳ ?"Ht F>6___PPT9 m 13.0& "  ""Z2 zRi h # lgֳgֳ ?"7 Ht F>6___PPT9 i 13.0& " |""_7  h # lgֳgֳ ?"H7 t  MAt 17 @`m  h # lgֳgֳ ?"HF>6___PPT9 m 15.8& "  ""Z2 zRi  h # lgֳgֳ ?"7 HF>6___PPT9 i 15.5& " |""_7  h # lgֳgֳ ?"7 H MAt 14 @`m  h # lgֳgֳ ?"F>6___PPT9 m 18.2& "  ""Z2 zRi h # lgֳgֳ ?"7 F>6___PPT9 i 18.9& " |""_7 h # lgֳgֳ ?"7  Q By age 13   @`i h # l0 gֳgֳ ?"}F>6___PPT9 iMen*(" EEZ2 zRe h # lgֳgֳ ?" }F>6___PPT9 eWomen( " x_7 h # lgֳgֳ ?"}  NOnset: @`B h Tgֳgֳ?"}}B h Tgֳgֳ?"  B h Tgֳgֳ?"} B h Tgֳgֳ?"} H h 0޽h ? 3380___PPT10.bP b%  M%E%P!!p$(  p~ p s *@}   $ `8  p# #""`8  W p # lgֳgֳ ?" `8 F>6___PPT9 W5.28(" &$W p # lgֳgֳ ?" 8 F>6___PPT9 W9.98(" &$X p # l,gֳgֳ ?"` 8 F>6___PPT9 X10.08(" &$X p # l1gֳgֳ ?" `8 F>6___PPT9 X14.98(" &$X p # l5gֳgֳ ?" 8 F>6___PPT9 X17.18(" &$X  p # l4gֳgֳ ?" 8 F>6___PPT9 X25.08(" &$c  p # l>gֳgֳ ?" 8 F>6___PPT9 c--6 years at risk6 " &$W  p # lAgֳgֳ ?"` F>6___PPT9 W2.78(" &$W  p # lDFgֳgֳ ?" F>6___PPT9 W6.38(" &$W  p # l Hgֳgֳ ?"` F>6___PPT9 W7.08(" &$W p # lNgֳgֳ ?" ` F>6___PPT9 W8.48(" &$W p # lQgֳgֳ ?"  F>6___PPT9 W7.78(" &$W p # l0Vgֳgֳ ?" F>6___PPT9 W8.08(" &$c p # l8Zgֳgֳ ?" F>6___PPT9 c--3 years at risk6 " &$W p # l^gֳgֳ ?"`F>6___PPT9 W19+8(" &$V p # lagֳgֳ ?"F>6___PPT9 V188(" &$V p # ldfgֳgֳ ?"`F>6___PPT9 V178(" &$V p # lljgֳgֳ ?" `F>6___PPT9 V168(" &$Y p # ltngֳgֳ ?"  F>6___PPT9 Y14-158(" &$V p # l|rgֳgֳ ?" F>6___PPT9 V138(" &$| p # lvgֳgֳ ?"F>6___PPT9 |Cumulative incidence6 " &$ @`Y p # lxgֳgֳ ?"`F>6___PPT9 YWomen8(" &$ p # lgֳgֳ ?" R$  @`B p Ngֳgֳ?"B p Ngֳgֳ?"8 `8 B p Ngֳgֳ?"8 B p Ngֳgֳ?"``B p Ngֳgֳ1?"`B  p Tgֳgֳ1 ?"`B !p Ngֳgֳ?"``8 H p 0޽h ? 3380___PPT10.bՙ   , $ `!!(  ~  s *~@}    `8  # #""`8    # lLgֳgֳ ?" `8  77.7  # llgֳgֳ ?" 8  813.6  # lqgֳgֳ ?"` 8  815.0  # lgֳgֳ ?" `8  821.1  # llgֳgֳ ?" 8  827.1   # lgֳgֳ ?" 8  837.0d   # lĨgֳgֳ ?" 8 F>6___PPT9 d--12 years at risk6 " &$   # lĭgֳgֳ ?"`  75.6   # lgֳgֳ ?"  813.3   # lgֳgֳ ?"`  812.5  # lgֳgֳ ?" `  819.3  # lgֳgֳ ?"   823.5  # lgֳgֳ ?"  830.0c  # lؽgֳgֳ ?" F>6___PPT9 c--9 years at risk6 " &$W  # lgֳgֳ ?"`F>6___PPT9 W19+8(" &$V  # lgֳgֳ ?"F>6___PPT9 V188(" &$V  # lgֳgֳ ?"`F>6___PPT9 V178(" &$V  # lgֳgֳ ?" `F>6___PPT9 V168(" &$Y  # lgֳgֳ ?"  F>6___PPT9 Y14-158(" &$V  # lgֳgֳ ?" F>6___PPT9 V138(" &$|  # lgֳgֳ ?"F>6___PPT9 |Cumulative incidence6 " &$ @`Y  # lgֳgֳ ?"`F>6___PPT9 YWomen8(" &$  # lgֳgֳ ?" R$  @`B  Ngֳgֳ?"B  Ngֳgֳ?"8 `8 B  Ngֳgֳ?"8 B  Ngֳgֳ?"``B  Ngֳgֳ1?"`B   Tgֳgֳ1 ?"`B ! Ngֳgֳ?"``8 H  0޽h ? 3380___PPT10.bՙF l pF(  x  c $<N     c $(}J  "8%!miH  0޽h ? 3380___PPT10.b`>  >(  x  c $з      c $p   H  0޽h ? 3380___PPT10.bP 0(%((   x ( #"2&cdccbdcx   f  ?"  x R 3.5; @`   f|  ?" x U 19 or later  " @`   f$ ?"   R 3.8; @`   fl*  ?"   L18" @`   fX, ?" O   R 3.5; @`   f:  ?"O  L17" @`    f< ?" O  R 4.0; @`    fJ  ?" O  L16" @`    fL ?"  R 4.7; @`    fZ  ?"  O14-15" @`    f\ ?" % R 4.6; @`   f,k  ?"%  Pd"13" @`#   fl| ?" % w-Lag until onset of alcohol dependence (years).. @`  # l{| ?" % j Age at onset of at-risk drinking!! @`   f} ?" OWomen @`B  Zgֳgֳo?"B  Zgֳgֳo?"x xB  Zgֳgֳo?"B  Zgֳgֳo?"B  Zgֳgֳo?"%B  Zgֳgֳo?"%B  Zgֳgֳo?"%B  Zgֳgֳo?"%B  Zgֳgֳo?"B  Zgֳgֳo?"B  Zgֳgֳo?"O B  Zgֳgֳo?"O B  Zgֳgֳo?"O  B  Zgֳgֳo?"O  B   Zgֳgֳo?"  B ! Zgֳgֳo?"  B " Zgֳgֳo?" xB # Zgֳgֳo?" xB $ Zgֳgֳo?" xxB % Tgֳgֳ1 ?"H  0޽h ? 3380___PPT10.b@PK .&%'(   > ' #"2&cdccbdc>   ft ?" > R 3.5; @`   fK  ?" > U 19 or later  " @`   f` ?" w   R 3.8; @`   f  ?"w  L18" @`   f ?"  w  R 3.7; @`   f  ?" w  L17" @`    f ?"   R 3.9; @`    f  ?"   L16" @`    f ?" O R 4.3; @`    f4  ?"O  O14-15" @`    f  ?" O R 5.4; @`   fd  ?" O Pd"13" @`#   f ?"  w-Lag until onset of alcohol dependence (years).. @`  # l ?"  j Age at onset of at-risk drinking!! @`   f  ?" MMen @`B  Zgֳgֳo?"B  Zgֳgֳo?"> >B  Zgֳgֳo?"B  Zgֳgֳo?"B  Zgֳgֳo?"B  Zgֳgֳo?"B  Zgֳgֳo?"OB  Zgֳgֳo?"OB  Zgֳgֳo?"OB  Zgֳgֳo?"OB  Zgֳgֳo?" B  Zgֳgֳo?" B  Zgֳgֳo?" w B  Zgֳgֳo?" w B   Zgֳgֳo?"w  B ! Zgֳgֳo?"w  B " Zgֳgֳo?" >B # Zgֳgֳo?" >B $ Zgֳgֳo?" >>B % Tgֳgֳ1 ?"H  0޽h ? 3380___PPT10.b@PKh  h(    # lgֳgֳA ? ?";|  r  S pN   H  0޽h ? 3380___PPT10.b0N m N(  x  c $N     c $$}J  *^6H  0޽h ? 3380___PPT10.b`$ n $(  r  S d+N   r  S  ,}J  H  0޽h ? 3380___PPT10.cPRjt s t(  r  S 82S     0X3` b.Women 6.5 Years (N=535) Men 6.6 Years (N=851)/ 2/H  0޽h ? 3380___PPT10.dp#K$ o $(  r  S (:N   r  S x:]  H  0޽h ? 3380___PPT10.cp !  (  x  c $X`   H  0޽h ? 3380___PPT10.b`ޅ" " /"'"**!(  ~  s *HB*Y   !   # #"."X     fDgֳgֳ ?"   S 29.8d @`   fMgֳgֳ ?"Z  S 29.0 @`   fP[gֳgֳ ?" Z  L19 @`   f<]gֳgֳ ?"   S 24.1d @`   f,egֳgֳ ?"Z  S 23.1 @`    flmgֳgֳ ?" Z  L15 @`    f|ugֳgֳ ?" x   S 16.6d @`    f}gֳgֳ ?"Zx  S 16.8 @`    f̅gֳgֳ ?"x Z  L10 @`    f܍gֳgֳ ?" Xx  S 10.9d @`   fgֳgֳ ?"ZX x  T 10.8  @`   f,gֳgֳ ?"XZx  K5 @`   f<gֳgֳ ?" 8X R 1.8d @`   fLgֳgֳ ?"Z8 X X 1.7@@   fgֳgֳ ?"8ZX K0 @`   f0gֳgֳ ?" 8 W Mother Report @`   ftgֳgֳ ?"Z 8 U Twin Report   @`   fgֳgֳ ?"Z8 PBy age @`   fgֳgֳ ?"Z dNeither parent alcoholic @`   fgֳgֳ ?"Z R  @`B  Zgֳgֳo?"ZB  Zgֳgֳo?" Z B  Zgֳgֳo?"B  Zgֳgֳo?"B  Zgֳgֳo?"ZB  Zgֳgֳo?"8B  Zgֳgֳo?"8B  Zgֳgֳo?"8XB   Zgֳgֳo?"8XB ! Zgֳgֳo?"Xx B " Zgֳgֳo?"Xx B # Zgֳgֳo?"x  B $ Zgֳgֳo?"x  B % Zgֳgֳo?"  B & Zgֳgֳo?"  B ' Zgֳgֳo?"  B ( Zgֳgֳo?"  B ) Zgֳgֳo?"Z B * Zgֳgֳo?"  H  0޽h ? 3380___PPT10.fO0" # "" *+!(      # #"."X     fgֳgֳ ?"   S 72.6d @`   fgֳgֳ ?"Z  S 60.0 @`   f gֳgֳ ?" Z  L19 @`   fgֳgֳ ?"   S 61.0d @`   fgֳgֳ ?"Z  S 51.9 @`    fgֳgֳ ?" Z  L15 @`    f'gֳgֳ ?" x   S 44.5d @`    f/gֳgֳ ?"Zx  S 36.3 @`    f<8gֳgֳ ?"x Z  L10 @`    fL@gֳgֳ ?" Xx  S 29.3d @`   f\Hgֳgֳ ?"ZX x  T 22.5  @`   fPgֳgֳ ?"XZx  K5 @`   fXgֳgֳ ?" 8X R 5.1d @`   fl`gֳgֳ ?"Z8 X X 3.3@@   fhgֳgֳ ?"8ZX K0 @`   fpgֳgֳ ?" 8 W Mother Report @`   fDxgֳgֳ ?"Z 8 U Twin Report   @`   fgֳgֳ ?"Z8 PBy age @`    fgֳgֳ ?"Z `One parent alcoholic @`   fgֳgֳ ?"Z R  @`B  Zgֳgֳo?"ZB  Zgֳgֳo?" Z B  Zgֳgֳo?"B  Zgֳgֳo?"B  Zgֳgֳo?"ZB  Zgֳgֳo?"8B  Zgֳgֳo?"8B  Zgֳgֳo?"8XB   Zgֳgֳo?"8XB ! Zgֳgֳo?"Xx B " Zgֳgֳo?"Xx B # Zgֳgֳo?"x  B $ Zgֳgֳo?"x  B % Zgֳgֳo?"  B & Zgֳgֳo?"  B ' Zgֳgֳo?"  B ( Zgֳgֳo?"  B ) Zgֳgֳo?"Z B * Zgֳgֳo?"  r + S DN   H  0޽h ? 3380___PPT10.fO0" $ ""0*+!(      # #"."X     fgֳgֳ ?"   S 75.6d @`   f̠gֳgֳ ?"Z  S 91.4 @`   f(gֳgֳ ?" Z  L19 @`   fgֳgֳ ?"   S 71.5d @`   f gֳgֳ ?"Z  S 73.7 @`    f`gֳgֳ ?" Z  L15 @`    fpgֳgֳ ?" x   S 50.4d @`    fgֳgֳ ?"Zx  S 52.5 @`    fgֳgֳ ?"x Z  L10 @`    fgֳgֳ ?" Xx  S 34.8d @`   fgֳgֳ ?"ZX x  S 45.9 @`   fgֳgֳ ?"XZx  K5 @`   f gֳgֳ ?" 8X R 9.8d @`   ftgֳgֳ ?"Z8 X X 6.6@@   f|gֳgֳ ?"8ZX K0 @`   f)gֳgֳ ?" 8 W Mother Report @`   f,2gֳgֳ ?"Z 8 U Twin Report   @`   f9gֳgֳ ?"Z8 PBy age @`    f`Bgֳgֳ ?"Z aTwo parents alcoholic @`   fJgֳgֳ ?"Z R  @`