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PMID: 23933821 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature genetics ·Vol. 45 ·No. 9 ·2013-09-00 ·Pages 984-94

Cross-Disorder Group of the Psychiatric Genomics Consortium, 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, International Inflammatory Bowel Disease Genetics Consortium IIBDGC

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.

MeSH Terms
Adult Attention Deficit Disorder with Hyperactivity/genetics Bipolar Disorder/genetics Child Child Development Disorders, Pervasive/genetics Crohn Disease/genetics Depressive Disorder, Major/genetics Genetic Heterogeneity Genetic Predisposition to Disease Genome, Human Genome-Wide Association Study Humans Inheritance Patterns Mental Disorders/genetics Polymorphism, Single Nucleotide Schizophrenia/genetics
Authors & Affiliations
372 authors, click to expand affiliations / ORCID
Cross-Disorder Group of the Psychiatric Genomics Consortium
The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia.
Lee S Hong
Ripke Stephan
Neale Benjamin M
Faraone Stephen V
Purcell Shaun M
Perlis Roy H
Mowry Bryan J
Thapar Anita
Goddard Michael E
Witte John S
Absher Devin
Agartz Ingrid
Akil Huda
Amin Farooq
Andreassen Ole A
Anjorin Adebayo
Anney Richard
Anttila Verneri
Arking Dan E
Asherson Philip
Azevedo Maria H
Backlund Lena
Badner Judith A
Bailey Anthony J
Banaschewski Tobias
Barchas Jack D
Barnes Michael R
Barrett Thomas B
Bass Nicholas
Battaglia Agatino
Bauer Michael
Bayés Mònica
Bellivier Frank
Bergen Sarah E
Berrettini Wade
Betancur Catalina
Bettecken Thomas
Biederman Joseph
Binder Elisabeth B
Black Donald W
Blackwood Douglas H R
Bloss Cinnamon S
Boehnke Michael
Boomsma Dorret I
Breen Gerome
Breuer René
Bruggeman Richard
Cormican Paul
Buccola Nancy G
Buitelaar Jan K
Bunney William E
Buxbaum Joseph D
Byerley William F
Byrne Enda M
Caesar Sian
Cahn Wiepke
Cantor Rita M
Casas Miguel
Chakravarti Aravinda
Chambert Kimberly
Choudhury Khalid
Cichon Sven
Cloninger C Robert
Collier David A
Cook Edwin H
Coon Hilary
Cormand Bru
Corvin Aiden
Coryell William H
Craig David W
Craig Ian W
Crosbie Jennifer
Cuccaro Michael L
Curtis David
Czamara Darina
Datta Susmita
Dawson Geraldine
Day Richard
De Geus Eco J
Degenhardt Franziska
Djurovic Srdjan
Donohoe Gary J
Doyle Alysa E
Duan Jubao
Dudbridge Frank
Duketis Eftichia
Ebstein Richard P
Edenberg Howard J
Elia Josephine
Ennis Sean
Etain Bruno
Fanous Ayman
Farmer Anne E
Ferrier I Nicol
Flickinger Matthew
Fombonne Eric
Foroud Tatiana
Frank Josef
Franke Barbara
Fraser Christine
Freedman Robert
Freimer Nelson B
Freitag Christine M
Friedl Marion
Frisén Louise
Gallagher Louise
Gejman Pablo V
Georgieva Lyudmila
Gershon Elliot S
Geschwind Daniel H
Giegling Ina
Gill Michael
Gordon Scott D
Gordon-Smith Katherine
Green Elaine K
Greenwood Tiffany A
Grice Dorothy E
Gross Magdalena
Grozeva Detelina
Guan Weihua
Gurling Hugh
De Haan Lieuwe
Haines Jonathan L
Hakonarson Hakon
Hallmayer Joachim
Hamilton Steven P
Hamshere Marian L
Hansen Thomas F
Hartmann Annette M
Hautzinger Martin
Heath Andrew C
Henders Anjali K
Herms Stefan
Hickie Ian B
Hipolito Maria
Hoefels Susanne
Holmans Peter A
Holsboer Florian
Hoogendijk Witte J
Hottenga Jouke-Jan
Hultman Christina M
Hus Vanessa
Ingason Andrés
Ising Marcus
Jamain Stéphane
Jones Edward G
Jones Ian
Jones Lisa
Tzeng Jung-Ying
Kähler Anna K
Kahn René S
Kandaswamy Radhika
Keller Matthew C
Kennedy James L
Kenny Elaine
Kent Lindsey
Kim Yunjung
Kirov George K
Klauck Sabine M
Klei Lambertus
Knowles James A
Kohli Martin A
Koller Daniel L
Konte Bettina
Korszun Ania
Krabbendam Lydia
Krasucki Robert
Kuntsi Jonna
Kwan Phoenix
Landén Mikael
Långström Niklas
Lathrop Mark
Lawrence Jacob
Lawson William B
Leboyer Marion
Ledbetter David H
Lee Phil H
Lencz Todd
Lesch Klaus-Peter
Levinson Douglas F
Lewis Cathryn M
Li Jun
Lichtenstein Paul
Lieberman Jeffrey A
Lin Dan-Yu
Linszen Don H
Liu Chunyu
Lohoff Falk W
Loo Sandra K
Lord Catherine
Lowe Jennifer K
Lucae Susanne
MacIntyre Donald J
Madden Pamela A F
Maestrini Elena
Magnusson Patrik K E
Mahon Pamela B
Maier Wolfgang
Malhotra Anil K
Mane Shrikant M
Martin Christa L
Martin Nicholas G
Mattheisen Manuel
Matthews Keith
Mattingsdal Morten
McCarroll Steven A
McGhee Kevin A
McGough James J
McGrath Patrick J
McGuffin Peter
McInnis Melvin G
McIntosh Andrew
McKinney Rebecca
McLean Alan W
McMahon Francis J
McMahon William M
McQuillin Andrew
Medeiros Helena
Medland Sarah E
Meier Sandra
Melle Ingrid
Meng Fan
Meyer Jobst
Middeldorp Christel M
Middleton Lefkos
Milanova Vihra
Miranda Ana
Monaco Anthony P
Montgomery Grant W
Moran Jennifer L
Moreno-De-Luca Daniel
Morken Gunnar
Morris Derek W
Morrow Eric M
Moskvina Valentina
Muglia Pierandrea
Mühleisen Thomas W
Muir Walter J
Müller-Myhsok Bertram
Murtha Michael
Myers Richard M
Myin-Germeys Inez
Neale Michael C
Nelson Stan F
Nievergelt Caroline M
Nikolov Ivan
Nimgaonkar Vishwajit
Nolen Willem A
Nöthen Markus M
Nurnberger John I
Nwulia Evaristus A
Nyholt Dale R
O'Dushlaine Colm
Oades Robert D
Olincy Ann
Oliveira Guiomar
Olsen Line
Ophoff Roel A
Osby Urban
Owen Michael J
Palotie Aarno
Parr Jeremy R
Paterson Andrew D
Pato Carlos N
Pato Michele T
Penninx Brenda W
Pergadia Michele L
Pericak-Vance Margaret A
Pickard Benjamin S
Pimm Jonathan
Piven Joseph
Posthuma Danielle
Potash James B
Poustka Fritz
Propping Peter
Puri Vinay
Quested Digby J
Quinn Emma M
Ramos-Quiroga Josep Antoni
Rasmussen Henrik B
Raychaudhuri Soumya
Rehnström Karola
Reif Andreas
Ribasés Marta
Rice John P
Rietschel Marcella
Roeder Kathryn
Roeyers Herbert
Rossin Lizzy
Rothenberger Aribert
Rouleau Guy
Ruderfer Douglas
Rujescu Dan
Sanders Alan R
Sanders Stephan J
Santangelo Susan L
Sergeant Joseph A
Schachar Russell
Schalling Martin
Schatzberg Alan F
Scheftner William A
Schellenberg Gerard D
Scherer Stephen W
Schork Nicholas J
Schulze Thomas G
Schumacher Johannes
Schwarz Markus
Scolnick Edward
Scott Laura J
Shi Jianxin
Shilling Paul D
Shyn Stanley I
Silverman Jeremy M
Slager Susan L
Smalley Susan L
Smit Johannes H
Smith Erin N
Sonuga-Barke Edmund J S
St Clair David
State Matthew
Steffens Michael
Steinhausen Hans-Christoph
Strauss John S
Strohmaier Jana
Stroup T Scott
Sutcliffe James S
Szatmari Peter
Szelinger Szabocls
Thirumalai Srinivasa
Thompson Robert C
Todorov Alexandre A
Tozzi Federica
Treutlein Jens
Uhr Manfred
van den Oord Edwin J C G
Van Grootheest Gerard
Van Os Jim
Vicente Astrid M
Vieland Veronica J
Vincent John B
Visscher Peter M
Walsh Christopher A
Wassink Thomas H
Watson Stanley J
Weissman Myrna M
Werge Thomas
Wienker Thomas F
Wijsman Ellen M
Willemsen Gonneke
Williams Nigel
Willsey A Jeremy
Witt Stephanie H
Xu Wei
Young Allan H
Yu Timothy W
Zammit Stanley
Zandi Peter P
Zhang Peng
Zitman Frans G
Zöllner Sebastian
Devlin Bernie
Kelsoe John R
Sklar Pamela
Daly Mark J
O'Donovan Michael C
Craddock Nicholas
Sullivan Patrick F
Smoller Jordan W
Kendler Kenneth S
Wray Naomi R
International Inflammatory Bowel Disease Genetics Consortium (IIBDGC)
Investigators
105 investigators, click to expand
Abraham Clara
Achkar Jean-Paul
Ahmad Tariq
Amininejad Leila
Anathakrishnan Ashwin N
Andersen Vibeke
Anderson Carl A
Andrews Jane M
Annese Vito
Baidoo Leonard
Balshun Tobias
Bampton Peter A
Barrett Jeffrey C
Bitton Alain
Boucher Gabrielle
Brand Stephan
Brant Steven R
Büning Carsten
Cho Judy H
Cichon Sven
Cleynen Isabelle
Cohain Ariella
D'Amato Mauro
Daly Mark J
Dejong Dirk
Devaney Kathy L
DeVos Martine
Dubinsky Marla
Duerr Richard H
Edwards Cathryn
Ellinghaus David
Essers Jonah
Ferguson Lynnette R
Franchimont Denis
Franke Andre
Fransen Karin
Gearry Richard
Georges Michel
Gieger Christian
Glas Jürgen
Goyette Philippe
Hakonarson Hakon
Haritunians Talin
Hart Alisa
Hawkey Chris
Hedl Matija
Hu Xinli
Hui Ken Y
Jostins Luke
Karlsen Tom H
Kugathasan Subra
Kupcinskas Limas
Latiano Anna
Laukens Debby
Lawrance Ian C
Lee James C
Lees Charles W
Louis Edouard
Mahy Gillian
Mansfield John
Mathew Christopher G
McGovern Dermot P
Mitrovic Mitja
Morgan Angharad R
Mowat Craig
Newman William
Ning Kaida
Palmieri Orazio
Parkes Miles
Ponsioen Cyriel Y
Potocnik Uros
Prescott Natalie J
Radford-Smith Graham
Raychaudhuri Soumya
Regueiro Miguel
Rioux John D
Ripke Stephan
Rotter Jerome I
Russell Richard K
Sanderson Jeremy D
Sans Miquel
Satsangi Jack
Schadt Eric E
Schreiber Stefan
Schumm L Phillip
Sharma Yashoda
Silverberg Mark S
Simms Lisa A
Spain Sarah L
Sventoraityte Jurgita
Targan Stephan R
Taylor Kent D
Theatre Emilie
Tremelling Mark
Vermeire Severine
Verspaget Hein W
Weersma Rinse K
Wei Zhi
Wijmenga Cisca
Wilson David C
Winkelmann Juliane
Xavier Ramnik J
Zeissig Sebastian
Zhang Bin
Zhao Hongyu
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
Published
2013-09-00
Epub
2013-00-11
Pages
984-94
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3800159
Subset
IM
Grants
NIMH NIH HHS · U01 MH085520 · United States
NIMH NIH HHS · R01 MH100027 · United States
NHGRI NIH HHS · T32 HG000040 · United States
NIMH NIH HHS · R01 MH041953 · United States
Chief Scientist Office · CZB/4/540 · United Kingdom
Chief Scientist Office · ETM/137 · United Kingdom
NIMH NIH HHS · R01 MH100141 · United States
Medical Research Council · G1000718 · United Kingdom
Medical Research Council · G0800675 · United Kingdom
Medical Research Council · G9810900 · United Kingdom
Medical Research Council · G0600329 · United Kingdom
NCI NIH HHS · R01 CA082659 · United States
NICHD NIH HHS · P50 HD055782 · United States
NIMH NIH HHS · K24 MH094614 · United States
NIAAA NIH HHS · K05 AA017688 · United States
NIMH NIH HHS · K99 MH101367 · United States
Medical Research Council · G1000708 · United Kingdom
Medical Research Council · G1000632 · United Kingdom
Medical Research Council · G0800759 · United Kingdom
Chief Scientist Office · ETM/75 · United Kingdom
Wellcome Trust · 090532 · United Kingdom
NIMH NIH HHS · R01 MH085548 · United States
Medical Research Council · G0701420 · United Kingdom
NIMH NIH HHS · R01 MH094400 · United States
NIMH NIH HHS · R01 MH094293 · United States
NIMH NIH HHS · R01 MH083094 · United States
Medical Research Council · G0601030 · United Kingdom
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