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Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.


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.

SUBMITTER: Cross-Disorder Group of the Psychiatric Genomics Consortium 

PROVIDER: S-EPMC3800159 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs.

Lee S Hong SH   Ripke Stephan S   Neale Benjamin M BM   Faraone Stephen V SV   Purcell Shaun M SM   Perlis Roy H RH   Mowry Bryan J BJ   Thapar Anita A   Goddard Michael E ME   Witte John S JS   Absher Devin D   Agartz Ingrid I   Akil Huda H   Amin Farooq F   Andreassen Ole A OA   Anjorin Adebayo A   Anney Richard R   Anttila Verneri V   Arking Dan E DE   Asherson Philip P   Azevedo Maria H MH   Backlund Lena L   Badner Judith A JA   Bailey Anthony J AJ   Banaschewski Tobias T   Barchas Jack D JD   Barnes Michael R MR   Barrett Thomas B TB   Bass Nicholas N   Battaglia Agatino A   Bauer Michael M   Bayés Mònica M   Bellivier Frank F   Bergen Sarah E SE   Berrettini Wade W   Betancur Catalina C   Bettecken Thomas T   Biederman Joseph J   Binder Elisabeth B EB   Black Donald W DW   Blackwood Douglas H R DH   Bloss Cinnamon S CS   Boehnke Michael M   Boomsma Dorret I DI   Breen Gerome G   Breuer René R   Bruggeman Richard R   Cormican Paul P   Buccola Nancy G NG   Buitelaar Jan K JK   Bunney William E WE   Buxbaum Joseph D JD   Byerley William F WF   Byrne Enda M EM   Caesar Sian S   Cahn Wiepke W   Cantor Rita M RM   Casas Miguel M   Chakravarti Aravinda A   Chambert Kimberly K   Choudhury Khalid K   Cichon Sven S   Cloninger C Robert CR   Collier David A DA   Cook Edwin H EH   Coon Hilary H   Cormand Bru B   Corvin Aiden A   Coryell William H WH   Craig David W DW   Craig Ian W IW   Crosbie Jennifer J   Cuccaro Michael L ML   Curtis David D   Czamara Darina D   Datta Susmita S   Dawson Geraldine G   Day Richard R   De Geus Eco J EJ   Degenhardt Franziska F   Djurovic Srdjan S   Donohoe Gary J GJ   Doyle Alysa E AE   Duan Jubao J   Dudbridge Frank F   Duketis Eftichia E   Ebstein Richard P RP   Edenberg Howard J HJ   Elia Josephine J   Ennis Sean S   Etain Bruno B   Fanous Ayman A   Farmer Anne E AE   Ferrier I Nicol IN   Flickinger Matthew M   Fombonne Eric E   Foroud Tatiana T   Frank Josef J   Franke Barbara B   Fraser Christine C   Freedman Robert R   Freimer Nelson B NB   Freitag Christine M CM   Friedl Marion M   Frisén Louise L   Gallagher Louise L   Gejman Pablo V PV   Georgieva Lyudmila L   Gershon Elliot S ES   Geschwind Daniel H DH   Giegling Ina I   Gill Michael M   Gordon Scott D SD   Gordon-Smith Katherine K   Green Elaine K EK   Greenwood Tiffany A TA   Grice Dorothy E DE   Gross Magdalena M   Grozeva Detelina D   Guan Weihua W   Gurling Hugh H   De Haan Lieuwe L   Haines Jonathan L JL   Hakonarson Hakon H   Hallmayer Joachim J   Hamilton Steven P SP   Hamshere Marian L ML   Hansen Thomas F TF   Hartmann Annette M AM   Hautzinger Martin M   Heath Andrew C AC   Henders Anjali K AK   Herms Stefan S   Hickie Ian B IB   Hipolito Maria M   Hoefels Susanne S   Holmans Peter A PA   Holsboer Florian F   Hoogendijk Witte J WJ   Hottenga Jouke-Jan JJ   Hultman Christina M CM   Hus Vanessa V   Ingason Andrés A   Ising Marcus M   Jamain Stéphane S   Jones Edward G EG   Jones Ian I   Jones Lisa L   Tzeng Jung-Ying JY   Kähler Anna K AK   Kahn René S RS   Kandaswamy Radhika R   Keller Matthew C MC   Kennedy James L JL   Kenny Elaine E   Kent Lindsey L   Kim Yunjung Y   Kirov George K GK   Klauck Sabine M SM   Klei Lambertus L   Knowles James A JA   Kohli Martin A MA   Koller Daniel L DL   Konte Bettina B   Korszun Ania A   Krabbendam Lydia L   Krasucki Robert R   Kuntsi Jonna J   Kwan Phoenix P   Landén Mikael M   Långström Niklas N   Lathrop Mark M   Lawrence Jacob J   Lawson William B WB   Leboyer Marion M   Ledbetter David H DH   Lee Phil H PH   Lencz Todd T   Lesch Klaus-Peter KP   Levinson Douglas F DF   Lewis Cathryn M CM   Li Jun J   Lichtenstein Paul P   Lieberman Jeffrey A JA   Lin Dan-Yu DY   Linszen Don H DH   Liu Chunyu C   Lohoff Falk W FW   Loo Sandra K SK   Lord Catherine C   Lowe Jennifer K JK   Lucae Susanne S   MacIntyre Donald J DJ   Madden Pamela A F PA   Maestrini Elena E   Magnusson Patrik K E PK   Mahon Pamela B PB   Maier Wolfgang W   Malhotra Anil K AK   Mane Shrikant M SM   Martin Christa L CL   Martin Nicholas G NG   Mattheisen Manuel M   Matthews Keith K   Mattingsdal Morten M   McCarroll Steven A SA   McGhee Kevin A KA   McGough James J JJ   McGrath Patrick J PJ   McGuffin Peter P   McInnis Melvin G MG   McIntosh Andrew A   McKinney Rebecca R   McLean Alan W AW   McMahon Francis J FJ   McMahon William M WM   McQuillin Andrew A   Medeiros Helena H   Medland Sarah E SE   Meier Sandra S   Melle Ingrid I   Meng Fan F   Meyer Jobst J   Middeldorp Christel M CM   Middleton Lefkos L   Milanova Vihra V   Miranda Ana A   Monaco Anthony P AP   Montgomery Grant W GW   Moran Jennifer L JL   Moreno-De-Luca Daniel D   Morken Gunnar G   Morris Derek W DW   Morrow Eric M EM   Moskvina Valentina V   Muglia Pierandrea P   Mühleisen Thomas W TW   Muir Walter J WJ   Müller-Myhsok Bertram B   Murtha Michael M   Myers Richard M RM   Myin-Germeys Inez I   Neale Michael C MC   Nelson Stan F SF   Nievergelt Caroline M CM   Nikolov Ivan I   Nimgaonkar Vishwajit V   Nolen Willem A WA   Nöthen Markus M MM   Nurnberger John I JI   Nwulia Evaristus A EA   Nyholt Dale R DR   O'Dushlaine Colm C   Oades Robert D RD   Olincy Ann A   Oliveira Guiomar G   Olsen Line L   Ophoff Roel A RA   Osby Urban U   Owen Michael J MJ   Palotie Aarno A   Parr Jeremy R JR   Paterson Andrew D AD   Pato Carlos N CN   Pato Michele T MT   Penninx Brenda W BW   Pergadia Michele L ML   Pericak-Vance Margaret A MA   Pickard Benjamin S BS   Pimm Jonathan J   Piven Joseph J   Posthuma Danielle D   Potash James B JB   Poustka Fritz F   Propping Peter P   Puri Vinay V   Quested Digby J DJ   Quinn Emma M EM   Ramos-Quiroga Josep Antoni JA   Rasmussen Henrik B HB   Raychaudhuri Soumya S   Rehnström Karola K   Reif Andreas A   Ribasés Marta M   Rice John P JP   Rietschel Marcella M   Roeder Kathryn K   Roeyers Herbert H   Rossin Lizzy L   Rothenberger Aribert A   Rouleau Guy G   Ruderfer Douglas D   Rujescu Dan D   Sanders Alan R AR   Sanders Stephan J SJ   Santangelo Susan L SL   Sergeant Joseph A JA   Schachar Russell R   Schalling Martin M   Schatzberg Alan F AF   Scheftner William A WA   Schellenberg Gerard D GD   Scherer Stephen W SW   Schork Nicholas J NJ   Schulze Thomas G TG   Schumacher Johannes J   Schwarz Markus M   Scolnick Edward E   Scott Laura J LJ   Shi Jianxin J   Shilling Paul D PD   Shyn Stanley I SI   Silverman Jeremy M JM   Slager Susan L SL   Smalley Susan L SL   Smit Johannes H JH   Smith Erin N EN   Sonuga-Barke Edmund J S EJ   St Clair David D   State Matthew M   Steffens Michael M   Steinhausen Hans-Christoph HC   Strauss John S JS   Strohmaier Jana J   Stroup T Scott TS   Sutcliffe James S JS   Szatmari Peter P   Szelinger Szabocls S   Thirumalai Srinivasa S   Thompson Robert C RC   Todorov Alexandre A AA   Tozzi Federica F   Treutlein Jens J   Uhr Manfred M   van den Oord Edwin J C G EJ   Van Grootheest Gerard G   Van Os Jim J   Vicente Astrid M AM   Vieland Veronica J VJ   Vincent John B JB   Visscher Peter M PM   Walsh Christopher A CA   Wassink Thomas H TH   Watson Stanley J SJ   Weissman Myrna M MM   Werge Thomas T   Wienker Thomas F TF   Wijsman Ellen M EM   Willemsen Gonneke G   Williams Nigel N   Willsey A Jeremy AJ   Witt Stephanie H SH   Xu Wei W   Young Allan H AH   Yu Timothy W TW   Zammit Stanley S   Zandi Peter P PP   Zhang Peng P   Zitman Frans G FG   Zöllner Sebastian S   Devlin Bernie B   Kelsoe John R JR   Sklar Pamela P   Daly Mark J MJ   O'Donovan Michael C MC   Craddock Nicholas N   Sullivan Patrick F PF   Smoller Jordan W JW   Kendler Kenneth S KS   Wray Naomi R NR  

Nature genetics 20130811 9


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 metho  ...[more]

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