Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs / Lee SH;Ripke S;Neale BM;Faraone SV;Purcell SM;Perlis RH;Mowry BJ;Thapar A;Goddard ME;Witte JS;Absher D;Agartz I;Akil H;Amin F;Andreassen OA;Anjorin A;Anney R;Anttila V;Arking DE;Asherson P;Azevedo MH;Backlund L;Badner JA;Bailey AJ;Banaschewski T;Barchas JD;Barnes MR;Barrett TB;Bass N;Battaglia A;Bauer M;Bayés M;Bellivier F;Bergen SE;Berrettini W;Betancur C;Bettecken T;Biederman J;Binder EB;Black DW;Blackwood DH;Bloss CS;Boehnke M;Boomsma DI;Breen G;Breuer R;Bruggeman R;Cormican P;Buccola NG;Buitelaar JK;Bunney WE;Buxbaum JD;Byerley WF;Byrne EM;Caesar S;Cahn W;Cantor RM;Casas M;Chakravarti A;Chambert K;Choudhury K;Cichon S;Cloninger CR;Collier DA;Cook EH;Coon H;Cormand B;Corvin A;Coryell WH;Craig DW;Craig IW;Crosbie J;Cuccaro ML;Curtis D;Czamara D;Datta S;Dawson G;Day R;De Geus EJ;Degenhardt F;Djurovic S;Donohoe GJ;Doyle AE;Duan J;Dudbridge F;Duketis E;Ebstein RP;Edenberg HJ;Elia J;Ennis S;Etain B;Fanous A;Farmer AE;Ferrier IN;Flickinger M;Fombonne E;Foroud T;Frank J;Franke B;Fraser C;Freedman R;Freimer NB;Freitag CM;Friedl M;Frisén L;Gallagher L;Gejman PV;Georgieva L;Gershon ES;Geschwind DH;Giegling I;Gill M;Gordon SD;Gordon-Smith K;Green EK;Greenwood TA;Grice DE;Gross M;Grozeva D;Guan W;Gurling H;De Haan L;Haines JL;Hakonarson H;Hallmayer J;Hamilton SP;Hamshere ML;Hansen TF;Hartmann AM;Hautzinger M;Heath AC;Henders AK;Herms S;Hickie IB;Hipolito M;Hoefels S;Holmans PA;Holsboer F;Hoogendijk WJ;Hottenga JJ;Hultman CM;Hus V;Ingason A;Ising M;Jamain S;Jones EG;Jones I;Jones L;Tzeng JY;Kähler AK;Kahn RS;Kandaswamy R;Keller MC;Kennedy JL;Kenny E;Kent L;Kim Y;Kirov GK;Klauck SM;Klei L;Knowles JA;Kohli MA;Koller DL;Konte B;Korszun A;Krabbendam L;Krasucki R;Kuntsi J;Kwan P;Landén M;Långström N;Lathrop M;Lawrence J;Lawson WB;Leboyer M;Ledbetter DH;Lee PH;Lencz T;Lesch KP;Levinson DF;Lewis CM;Li J;Lichtenstein P;Lieberman JA;Lin DY;Linszen DH;Liu C;Lohoff FW;Loo SK;Lord C;Lowe JK;Lucae S;MacIntyre DJ;Madden PA;Maestrini E;Magnusson PK;Mahon PB;Maier W;Malhotra AK;Mane SM;Martin CL;Martin NG;Mattheisen M;Matthews K;Mattingsdal M;McCarroll SA;McGhee KA;McGough JJ;McGrath PJ;McGuffin P;McInnis MG;McIntosh A;McKinney R;McLean AW;McMahon FJ;McMahon WM;McQuillin A;Medeiros H;Medland SE;Meier S;Melle I;Meng F;Meyer J;Middeldorp CM;Middleton L;Milanova V;Miranda A;Monaco AP;Montgomery GW;Moran JL;Moreno-De-Luca D;Morken G;Morris DW;Morrow EM;Moskvina V;Muglia P;Mühleisen TW;Muir WJ;Müller-Myhsok B;Murtha M;Myers RM;Myin-Germeys I;Neale MC;Nelson SF;Nievergelt CM;Nikolov I;Nimgaonkar V;Nolen WA;Nöthen MM;Nurnberger JI;Nwulia EA;Nyholt DR;O'Dushlaine C;Oades RD;Olincy A;Oliveira G;Olsen L;Ophoff RA;Osby U;Owen MJ;Palotie A;Parr JR;Paterson AD;Pato CN;Pato MT;Penninx BW;Pergadia ML;Pericak-Vance MA;Pickard BS;Pimm J;Piven J;Posthuma D;Potash JB;Poustka F;Propping P;Puri V;Quested DJ;Quinn EM;Ramos-Quiroga JA;Rasmussen HB;Raychaudhuri S;Rehnström K;Reif A;Ribasés M;Rice JP;Rietschel M;Roeder K;Roeyers H;Rossin L;Rothenberger A;Rouleau G;Ruderfer D;Rujescu D;Sanders AR;Sanders SJ;Santangelo SL;Sergeant JA;Schachar R;Schalling M;Schatzberg AF;Scheftner WA;Schellenberg GD;Scherer SW;Schork NJ;Schulze TG;Schumacher J;Schwarz M;Scolnick E;Scott LJ;Shi J;Shilling PD;Shyn SI;Silverman JM;Slager SL;Smalley SL;Smit JH;Smith EN;Sonuga-Barke EJ;St Clair D;State M;Steffens M;Steinhausen HC;Strauss JS;Strohmaier J;Stroup TS;Sutcliffe JS;Szatmari P;Szelinger S;Thirumalai S;Thompson RC;Todorov AA;Tozzi F;Treutlein J;Uhr M;van den Oord EJ;Van Grootheest G;Van Os J;Vicente AM;Vieland VJ;Vincent JB;Visscher PM;Walsh CA;Wassink TH;Watson SJ;Weissman MM;Werge T;Wienker TF;Wijsman EM;Willemsen G;Williams N;Willsey AJ;Witt SH;Xu W;Young AH;Yu TW;Zammit S;Zandi PP;Zhang P;Zitman FG;Zöllner S;Devlin B;Kelsoe JR;Sklar P;Daly MJ;O'Donovan MC;Craddock N;Sullivan PF;Smoller JW;Kendler KS;Wray NR;Cross-Disorder Group of the Psychiatric Genomics Consortium;International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). - In: NATURE GENETICS. - ISSN 1061-4036. - STAMPA. - 45:(2013), pp. 984-994. [10.1038/ng.2711]
Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.
MAESTRINI, ELENA;
2013
Abstract
Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
