Genome-wide association study identifies 30 loci associated with bipolar disorder

Nature Genetics

Volumn 51, Issue 5, 2019, Pages 793-803

  Stahl, Eli A ^a,b   Breen, Gerome ^c,d   Forstner, Andreas J ^e,f,g,h,i   McQuillin, Andrew ^j   Ripke, Stephan ^b,k,l   Trubetskoy, Vassily ^k   Mattheisen, Manuel ^m,n,o,p   Wang, Yunpeng ^q,r   Coleman, Jonathan R I ^c,d   Gaspar, Héléna A ^c,d   de Leeuw, Christiaan A ^s   Steinberg, Stacy ^t   Pavlides, Jennifer M Whitehead ^u   Trzaskowski, Maciej ^u   Byrne, Enda M ^u   Pers, Tune H ^b,v   Holmans, Peter A ^w   Richards, Alexander L ^w   Abbott, Liam ^b   Agerbo, Esben ^m,p   Akil, Huda ^x   Albani, Diego ^y   Alliey Rodriguez, Ney ^z   Als, Thomas D ^m,p   Anjorin, Adebayo ^aa   Antilla, Verneri ^l   Awasthi, Swapnil ^k   Badner, Judith A ^ab   Bækvad Hansen, Marie ^p,ac   Barchas, Jack D ^ad   Bass, Nicholas ^j   Bauer, Michael ^ae   Belliveau, Richard ^b   Bergen, Sarah E ⁿ   Pedersen, Carsten Bøcker ^m,p   Bøen, Erlend ^af   Boks, Marco P ^ag   Boocock, James ^ah   Budde, Monika ^ai   Bunney, William ^aj   Burmeister, Margit ^ak   Bybjerg Grauholm, Jonas ^p,ac   Byerley, William ^al   Casas, Miquel ^am,an,ao   Cerrato, Felecia ^b   Cervantes, Pablo ^ap   Chambert, Kimberly ^b   Charney, Alexander W ^a   Chen, Danfeng ^b   Churchhouse, Claire ^b,l   Clarke, Toni Kim ^aq   Coryell, William ^ar   Craig, David W ^as   Cruceanu, Cristiana ^ap,at   Curtis, David ^j,au   Czerski, Piotr M ^av   Dale, Anders M ^aw,ax,ay   de Jong, Simone ^c,d   Degenhardt, Franziska ^g   Del Favero, Jurgen ^az   DePaulo, J Raymond ^ba   Djurovic, Srdjan ^bb,bc   Dobbyn, Amanda L ^a   Dumont, Ashley ^b   Elvsåshagen, Torbjørn ^bd   Escott Price, Valentina ^w   Fan, Chun Chieh ^ay   Fischer, Sascha B ^e,i   Flickinger, Matthew ^be   Foroud, Tatiana M ^bf   Forty, Liz ^w   Frank, Josef ^bg   Fraser, Christine ^w   Freimer, Nelson B ^bh   Frisén, Louise ^bi,bj   Gade, Katrin ^ai,bk   Gage, Diane ^b   Garnham, Julie ^bl   Giambartolomei, Claudia ^ah   Pedersen, Marianne Giørtz ^m,p   Goldstein, Jaqueline ^b   Gordon, Scott D ^bm   Gordon Smith, Katherine ^bn   Green, Elaine K ^bo   Green, Melissa J ^bp,bq   Greenwood, Tiffany A ^ax   Grove, Jakob ^m,p   Guan, Weihua ^br   Guzman Parra, José ^bs   Hamshere, Marian L ^w   Hautzinger, Martin ^bt   Heilbronner, Urs ^ai   Herms, Stefan ^e,g,i   Hipolito, Maria ^bu   Hoffmann, Per ^e,g,i   Holland, Dominic ^aw,ax   Huckins, Laura ^a   Jamain, Stéphane ^bv,bw   Johnson, Jessica S ^a   Juréus, Anders ⁿ   Kandaswamy, Radhika ^c   Karlsson, Robert ⁿ   Kennedy, James L ^bx,by,bz   Kittel Schneider, Sarah ^ca   Knowles, James A ^cb   Kogevinas, Manolis ^cc   Koller, Anna C ^g   Kupka, Ralph ^cd,ce,cf   Lavebratt, Catharina ^bi   Lawrence, Jacob ^cg   Lawson, William B ^bu   Leber, Markus ^g   Lee, Phil H ^b,l   Levy, Shawn E ^ch   Li, Jun Z ^ak   Liu, Chunyu ^ci   Lucae, Susanne ^at   Maaser, Anna ^g   MacIntyre, Donald J ^cj,ck   Mahon, Pamela B ^ba,cl   Maier, Wolfgang ^cm   Martinsson, Lina ^bi   McCarroll, Steve ^b,cn   McGuffin, Peter ^c   McInnis, Melvin G ^be   McKay, James D ^co   Medeiros, Helena ^cb   Medland, Sarah E ^bm   Meng, Fan ^x,be   Milani, Lili ^cp   Montgomery, Grant W ^u   Morris, Derek W ^cq,cr   Mühleisen, Thomas W ^e,cs   Mullins, Niamh ^c   Nguyen, Hoang ^a   Nievergelt, Caroline M ^ax,ct   Adolfsson, Annelie Nordin ^cu   Nwulia, Evaristus A ^bu   O’Donovan, Claire ^bl   Loohuis, Loes M Olde ^bh   Ori, Anil P S ^bh   Oruc, Lilijana ^cv   Ösby, Urban ^bi   Perlis, Roy H ^l,cn   Perry, Amy ^bn   Pfennig, Andrea ^ae   Potash, James B ^ba   Purcell, Shaun M ^a,cl   Regeer, Eline J ^cw   Reif, Andreas ^ca   Reinbold, Céline S ^e,i   Rice, John P ^cx   Rivas, Fabio ^bs   Rivera, Margarita ^c,cy   Roussos, Panos ^a   Ruderfer, Douglas M ^cz   Ryu, Euijung ^da   Sánchez Mora, Cristina ^am,an,ao   Schatzberg, Alan F ^db   Scheftner, William A ^ab   Schork, Nicholas J ^dc   Shannon Weickert, Cynthia ^bp,bq   Shehktman, Tatyana ^ax   Shilling, Paul D ^ax   Sigurdsson, Engilbert ^dd   Slaney, Claire ^bl   Smeland, Olav B ^r,bd   Sobell, Janet L ^de   Søholm Hansen, Christine ^p,ac   Spijker, Anne T ^df   St Clair, David ^dg   Steffens, Michael ^dh   Strauss, John S ^bx,by   Streit, Fabian ^bg   Strohmaier, Jana ^bg   Szelinger, Szabolcs ^as   Thompson, Robert C ^be   Thorgeirsson, Thorgeir E ^t   Treutlein, Jens ^bg   Vedder, Helmut ^di   Wang, Weiqing ^a   Watson, Stanley J ^be   Weickert, Thomas W ^bp,bq   Witt, Stephanie H ^bg   Xi, Simon ^dj   Xu, Wei ^by,dk   Young, Allan H ^d   Zandi, Peter ^dl   Zhang, Peng ^ba   Zöllner, Sebastian ^be   Adolfsson, Rolf ^cu   Agartz, Ingrid ^n,r,af   Alda, Martin ^bl,dm   Backlund, Lena ^bi   Baune, Bernhard T ^dn,do   Bellivier, Frank ^dp,dq,dr,ds   Berrettini, Wade H ^dt   Biernacka, Joanna M ^da   Blackwood, Douglas H R ^aq   Boehnke, Michael ^be   Børglum, Anders D ^m,p   Corvin, Aiden ^cr   Craddock, Nicholas ^w   Daly, Mark J ^b,l   Dannlowski, Udo ^do   Esko, Tõnu ^b,v,cn,cp   Etain, Bruno ^d,dp,dr,ds   Frye, Mark ^da   Fullerton, Janice M ^bp,bq   Gershon, Elliot S ^z   Gill, Michael ^cr   Goes, Fernando ^ba   Grigoroiu Serbanescu, Maria ^du   Hauser, Joanna ^av   Hougaard, David M ^p,ac   Hultman, Christina M ⁿ   Jones, Ian ^w   Jones, Lisa A ^bn   Kahn, René S ^a,ag   Kirov, George ^w   Landén, Mikael ^n,dv   Leboyer, Marion ^bw,dp,dr   Lewis, Cathryn M ^c,d   Li, Qingqin S ^dw   Lissowska, Jolanta ^dx   Martin, Nicholas G ^u,bm   Mayoral, Fermin ^bs   McElroy, Susan L ^dy   McIntosh, Andrew M ^aq   McMahon, Francis J ^dz   Melle, Ingrid ^bd   Metspalu, Andres ^cp,ea   Mitchell, Philip B ^bp   Morken, Gunnar ^eb,ec   Mors, Ole ^p,ed   Mortensen, Preben Bo ^m,p   Müller Myhsok, Bertram ^at,ee,ef   Myers, Richard M ^ch   Neale, Benjamin M ^b,l   Nimgaonkar, Vishwajit ^eg   Nordentoft, Merete ^p,eh   Nöthen, Markus M ^g   O’Donovan, Michael C ^w   Oedegaard, Ketil J ^bc,ei   Owen, Michael J ^w   Paciga, Sara A ^dj   Pato, Carlos ^cb   Pato, Michele T ^cb   Posthuma, Danielle ^s,ej   Ramos Quiroga, Josep Antoni ^am,an,ao   Ribasés, Marta ^am,an,ao   Rietschel, Marcella ^bg   Rouleau, Guy A ^ek,el   Schalling, Martin ^bi   Schofield, Peter R ^bp,bq   Schulze, Thomas G ^{ai,ba,bg,bk,dz}   Serretti, Alessandro ^em   Smoller, Jordan W ^b,l   Stefansson, Hreinn ^t   Stefansson, Kari ^t,dd   Stordal, Eystein ^eb,en   Sullivan, Patrick F ^n,eo   Turecki, Gustavo ^ek   Vaaler, Arne E ^ec   Vieta, Eduard ^ep   Vincent, John B ^bx   Werge, Thomas ^p,eh,eq   Nurnberger, John I ^er   Wray, Naomi R ^u   Di Florio, Arianna ^w,eo   Edenberg, Howard J ^er   Cichon, Sven ^e,g,i,cs   Ophoff, Roel A ^ag,ah,bh   Scott, Laura J ^be   Andreassen, Ole A ^r,bd   Kelsoe, John ^ax   Sklar, Pamela ^a,ba   more..

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^c MEDICAL RESEARCH COUNCIL   (United Kingdom)

^d KING'S COLLEGE LONDON   (United Kingdom)

^e UNIVERSITY OF BASEL   (Switzerland)

^f UNIVERSITY OF BASEL   (Switzerland)

^g UNIVERSITY HOSPITAL BONN   (Germany)

^h PHILIPPS UNIVERSITY MARBURG   (Germany)

ⁱ UNIVERSITY HOSPITAL BASEL   (Switzerland)

^j UNIVERSITY COLLEGE LONDON   (United Kingdom)

^k CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^l MASSACHUSETTS GENERAL HOSPITAL   (United States)

^m AARHUS UNIVERSITY   (Denmark)

ⁿ KAROLINSKA INSTITUTE   (Sweden)

^o UNIVERSITY HOSPITAL WÜRZBURG   (Germany)

^p Lundbeck Foundation Initiative for Integrative Psychiatric Research   (Denmark)

^q Mental Health Centre Sct Hans   (Denmark)

^r UNIVERSITY OF OSLO   (Norway)

^s VU UNIVERSITY AMSTERDAM   (Netherlands)

^t DECODE GENETICS   (Iceland)

^u UNIVERSITY OF QUEENSLAND   (Australia)

^v BOSTON CHILDREN S HOSPITAL   (United States)

^w CARDIFF UNIVERSITY   (United Kingdom)

^x UNIVERSITY OF MICHIGAN   (United States)

^y MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^z UNIVERSITY OF CHICAGO   (United States)

^aa BERKSHIRE HEALTHCARE NHS FOUNDATION TRUST   (United Kingdom)

^ab RUSH UNIVERSITY MEDICAL CENTER   (United States)

^ac STATENS SERUM INSTITUT   (Denmark)

^ad WEILL CORNELL MEDICAL COLLEGE   (United States)

^ae UNIVERSITY HOSPITAL CARL GUSTAV CARUS   (Germany)

^af DIAKONHJEMMET HOSPITAL   (Norway)

^ag UNIVERSITY MEDICAL CENTER UTRECHT   (Netherlands)

^ah UNIVERSITY OF CALIFORNIA   (United States)

^ai LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^aj UNIVERSITY OF CALIFORNIA   (United States)

^ak UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^al UNIVERSITY OF CALIFORNIA   (United States)

^am CENTRO DE INVESTIGACIÓN BIOMÉDICA EN RED DE SALUD MENTAL CIBERSAM   (Spain)

^an HOSPITAL UNIVERSITARI VALL D HEBRON   (Spain)

^ao UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^ap MCGILL UNIVERSITY HEALTH CENTRE   (Canada)

^aq UNIVERSITY OF EDINBURGH   (United Kingdom)

^ar UNIVERSITY OF IOWA HOSPITALS AND CLINICS   (United States)

^as TRANSLATIONAL GENOMICS RESEARCH INSTITUTE   (United States)

^at MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

^au QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^av POZNAN UNIVERSITY OF MEDICAL SCIENCES   (Poland)

^aw UNIVERSITY OF CALIFORNIA   (United States)

^ax UNIVERSITY OF CALIFORNIA   (United States)

^ay UNIVERSITY OF CALIFORNIA   (United States)

^az UNIVERSITY OF ANTWERP   (Belgium)

^ba JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^bb ULLEVÅL UNIVERSITY HOSPITAL   (Norway)

^bc UNIVERSITY OF BERGEN   (Norway)

^bd OSLO UNIVERSITY HOSPITAL   (Norway)

^be UNIVERSITY OF MICHIGAN   (United States)

^bf INDIANA UNIVERSITY   (United States)

^bg UNIVERSITY OF HEIDELBERG   (Germany)

^bh UNIVERSITY OF CALIFORNIA   (United States)

^bi KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^bj Child and Adolescent Psychiatry Research Center   (Sweden)

^bk UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^bl DALHOUSIE UNIVERSITY   (Canada)

^bm QIMR BERGHOFER MEDICAL RESEARCH INSTITUTE   (Australia)

^bn UNIVERSITY OF WORCESTER   (United Kingdom)

^bo PLYMOUTH UNIVERSITY PENINSULA SCHOOLS OF MEDICINE AND DENTISTRY   (United Kingdom)

^bp UNIVERSITY OF NEW SOUTH WALES   (Australia)

^bq NEUROSCIENCE RESEARCH AUSTRALIA   (Australia)

^br UNIVERSITY OF MINNESOTA   (United States)

^bs University Regional Hospital   (Spain)

^bt UNIVERSITY OF TÜBINGEN   (Germany)

^bu HOWARD UNIVERSITY HOSPITAL   (United States)

^bv INSERM U955   (France)

^bw FACULTÉ DE MÉDECINE   (France)

^bx CENTRE FOR ADDICTION AND MENTAL HEALTH   (Canada)

^by UNIVERSITY OF TORONTO   (Canada)

^bz UNIVERSITY OF TORONTO   (Canada)

^ca UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^cb Downstate Health Sciences University   (United States)

^cc CENTRE FOR RESEARCH IN ENVIRONMENTAL EPIDEMIOLOGY CREAL   (Spain)

^cd Afdeling Psychiatrie   (Netherlands)

^ce GGZ inGeest   (Netherlands)

^cf VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^cg EAST LONDON NHS FOUNDATION TRUST   (United Kingdom)

^ch HUDSONALPHA INSTITUTE FOR BIOTECHNOLOGY   (United States)

^ci UNIVERSITY OF ILLINOIS   (United States)

^cj HEALTHCARE IMPROVEMENT SCOTLAND   (United Kingdom)

^ck UNIVERSITY OF EDINBURGH   (United Kingdom)

^cl BRIGHAM AND WOMEN S HOSPITAL   (United States)

^cm UNIVERSITY OF BONN   (Germany)

^cn HARVARD MEDICAL SCHOOL   (United States)

^co INTERNATIONAL AGENCY FOR RESEARCH ON CANCER   (France)

^cp UNIVERSITY OF TARTU   (Estonia)

^cq NATIONAL UNIVERSITY OF IRELAND   (Ireland)

^cr TRINITY COLLEGE DUBLIN   (Ireland)

^cs FORSCHUNGSZENTRUM JÜLICH   (Germany)

^ct VA SAN DIEGO HEALTHCARE SYSTEM   (United States)

^cu UMEÅ UNIVERSITY   (Sweden)

^cv UNIVERSITY OF SARAJEVO   (Bosnia and Herzegovina)

^cw Outpatient Clinic for Bipolar Disorder   (Netherlands)

^cx WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^cy UNIVERSITY OF GRANADA   (Spain)

^cz VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

^da MAYO CLINIC   (United States)

^db STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^dc SCRIPPS TRANSLATIONAL SCIENCE INSTITUTE   (United States)

^dd UNIVERSITY OF ICELAND   (Iceland)

^de UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

^df PsyQ   (Netherlands)

^dg UNIVERSITY OF ABERDEEN   (United Kingdom)

^dh Federal Institute for Drugs and Medical Devices   (Germany)

^di Psychiatrisches Zentrum   (Germany)

^dj PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

^dk PRINCESS MARGARET HOSPITAL   (Canada)

^dl JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

^dm NATIONAL INSTITUTE OF MENTAL HEALTH   (Czech Republic)

^dn UNIVERSITY OF MELBOURNE   (Australia)

^do UNIVERSITY OF MÜNSTER   (Germany)

^dp ASSISTANCE PUBLIQUE HÔPITAUX DE PARIS   (France)

^dq FONDATION FONDAMENTAL   (France)

^dr INSERM   (France)

^ds UNIVERSITÉ PARIS DESCARTES   (France)

^dt UNIVERSITY OF PENNSYLVANIA   (United States)

^du Psychiatric Hospital Bucharest   (Romania)

^dv UNIVERSITY OF GOTHENBURG   (Sweden)

^dw JANSSEN RESEARCH AND DEVELOPMENT   (United States)

^dx INSTITUTE OF ONCOLOGY   (Poland)

^dy LINDNER CENTER OF HOPE   (United States)

^dz NATIONAL INSTITUTE OF MENTAL HEALTH   (United States)

^ea UNIVERSITY OF TARTU   (Estonia)

^eb NORWEGIAN UNIVERSITY OF SCIENCE AND TECHNOLOGY   (Norway)

^ec TRONDHEIM UNIVERSITY HOSPITAL   (Norway)

^ed AARHUS UNIVERSITY HOSPITAL   (Denmark)

^ee Technische Universität München Munich Cluster for Systems Neurology   (Germany)

^ef UNIVERSITY OF LIVERPOOL   (United Kingdom)

^eg UNIVERSITY OF PITTSBURGH   (United States)

^eh UNIVERSITY OF COPENHAGEN   (Denmark)

^ei HAUKELAND UNIVERSITY HOSPITAL   (Norway)

^ej Montreal Neurological Institute and Hospital ^*  (Netherlands)

^ek MCGILL UNIVERSITY   (Canada)

^el MCGILL UNIVERSITY   (Canada)

^em UNIVERSITY OF BOLOGNA   (Italy)

^en Namsos Hospital   (Norway)

^eo UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^ep UNIVERSITY OF BARCELONA   (Spain)

^eq Psychiatric Centre Sct Hans   (Denmark)

^er INDIANA UNIVERSITY SCHOOL OF MEDICINE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ADCY2 PROTEIN; ADD3 PROTEIN; CACNA1C PROTEIN; CD47 ANTIGEN; ENDOCANNABINOID; FADS2 PROTEIN; FSTL5 PROTEIN; HISTONE DEACETYLASE 5; INSULIN; ION CHANNEL; ITIH1 PROTEIN; LMAN2L PROTEIN; MRPS33 PROTEIN; N METHYL DEXTRO ASPARTIC ACID RECEPTOR 2A; NCAN PROTEIN; NEUROTRANSMITTER TRANSPORTER; PACS1 PROTEIN; PLEKHO1 PROTEIN; POU3F2 PROTEIN; RPS6KA2 PROTEIN; SHANK2 PROTEIN; SODIUM CHANNEL NAV1.2; SRPK2 PROTEIN; SSBP2 PROTEIN; STARD9 PROTEIN; TFAP2B PROTEIN; THSD7A PROTEIN; TRANK1 PROTEIN; UNCLASSIFIED DRUG; ZCCHC2 PROTEIN; ZNF592 PROTEIN;

ARTICLE; BIPOLAR DISORDER; BIPOLAR I DISORDER; BIPOLAR II DISORDER; COHORT ANALYSIS; COMPARATIVE STUDY; CONTROLLED STUDY; FOLLOW UP; GENE EXPRESSION; GENE FREQUENCY; GENE IDENTIFICATION; GENE LOCUS; GENETIC CORRELATION; GENETIC HETEROGENEITY; GENETIC TRAIT; GENETIC VARIABILITY; GENOME-WIDE ASSOCIATION STUDY; HUMAN; INSULIN RELEASE; MAJOR CLINICAL STUDY; MAJOR DEPRESSION; MOLECULAR PATHOLOGY; PRIORITY JOURNAL; REGULATORY MECHANISM; SCHIZOPHRENIA; SYSTEMS BIOLOGY; CASE CONTROL STUDY; CLASSIFICATION; FEMALE; GENETIC PREDISPOSITION; GENETICS; MALE; META ANALYSIS; PSYCHOSIS; SINGLE NUCLEOTIDE POLYMORPHISM;

BIPOLAR DISORDER; CASE-CONTROL STUDIES; DEPRESSIVE DISORDER, MAJOR; FEMALE; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; HUMANS; MALE; POLYMORPHISM, SINGLE NUCLEOTIDE; PSYCHOTIC DISORDERS; SCHIZOPHRENIA; SYSTEMS BIOLOGY;

EID: 85065180508     PISSN: 10614036     EISSN: 15461718     Source Type: Journal    
DOI: 10.1038/s41588-019-0397-8     Document Type: Article

References (76)

1. Ferrari, A. J. et al. The prevalence and burden of bipolar disorder: findings from the global burden of disease study 2013. Bipolar Disord. 18, 440–450 (2016).
2. Lichtenstein, P. et al. Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373, 234–239 (2009).
3. Edvardsen, J. et al. Heritability of bipolar spectrum disorders. Unity or heterogeneity? J. Affect. Disord. 106, 229–240 (2008).
4. McGuffin, P. et al. The heritability of bipolar affective disorder and the genetic relationship to unipolar depression. Arch. Gen. Psychiatry 60, 497–502 (2003).
5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 5th edn (American Psychiatric Association Publishing, 2013).
6. World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines (World Health Organization, 1992).
7. Craddock, N. & Owen, M. J. The Kraepelinian dichotomy—going, going… but still not gone. Br. J. Psychiatry 196, 92–95 (2010).
8. Lee, S. H. et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 45, 984–994 (2013).
9. Sklar, P. et al. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat. Genet. 43, 977–983 (2011).
10. Baum, A. E. et al. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol. Psychiatry 13, 197–207 (2008).
11. Charney, A. W. et al. Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder. Transl. Psychiatry 7, e993 (2017).
12. Chen, D. T. et al. Genome-wide association study meta-analysis of European and Asian-ancestry samples identifies three novel loci associated with bipolar disorder. Mol. Psychiatry 18, 195–205 (2013).
13. Cichon, S. et al. Genome-wide association study identifies genetic variation in neurocan as a susceptibility factor for bipolar disorder. Am. J. Hum. Genet. 88, 372–381 (2011).
14. Ferreira, M. A. R. et al. Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat. Genet. 40, 1056–1058 (2008).
15. Green, E. K. et al. Association at SYNE1 in both bipolar disorder and recurrent major depression. Mol. Psychiatry 18, 614–617 (2013).
16. Green, E. K. et al. Replication of bipolar disorder susceptibility alleles and identification of two novel genome-wide significant associations in a new bipolar disorder case-control sample. Mol. Psychiatry 18, 1302–1307 (2013).
17. Hou, L. et al. Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder. Hum. Mol. Genet. 25, 3383–3394 (2016).
18. Mühleisen, T. W. et al. Genome-wide association study reveals two new risk loci for bipolar disorder. Nat. Commun. 5, 3339 (2014).
19. Schulze, T. G. et al. Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder. Mol. Psychiatry 14, 487–491 (2009).
20. Scott, L. J. et al. Genome-wide association and meta-analysis of bipolar disorder in individuals of European ancestry. Proc. Natl Acad. Sci. USA 106, 7501–7506 (2009).
21. Sklar, P. et al. Whole-genome association study of bipolar disorder. Mol. Psychiatry 13, 558–569 (2008).
22. Smith, E. N. et al. Genome-wide association study of bipolar disorder in European American and African American individuals. Mol. Psychiatry 14, 755–763 (2009).
23. Burton, P. R. et al. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).
24. Gratten, J., Wray, N. R., Keller, M. C. & Visscher, P. M. Large-scale genomics unveils the genetic architecture of psychiatric disorders. Nat. Neurosci. 17, 782–790 (2014).
25. Bulik-Sullivan, B. K. et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291–295 (2015).
26. Zheng, J. et al. LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics 33, 272–279 (2017).
27. Palmer, C. & Pe’er, I. Statistical correction of the winner’s curse explains replication variability in quantitative trait genome-wide association studies. PLoS Genet. 13, e1006916 (2017).
28. Zhong, H. & Prentice, R. L. Bias-reduced estimators and confidence intervals for odds ratios in genome-wide association studies. Biostatistics 9, 621–634 (2008).
29. Holland, D. et al. Beyond SNP heritability: polygenicity and discoverability estimated for multiple phenotypes with a univariate gaussian mixture model. Preprint at biorXiv 10.1101/133132 (2018).
30. Gao, X., Starmer, J. & Martin, E. R. A multiple testing correction method for genetic association studies using correlated single nucleotide polymorphisms. Genet. Epidemiol. 32, 361–369 (2008).
31. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511, 421–427 (2014).
32. Ripke, S. et al. Genome-wide association analysis identifies 13 new risk loci for schizophrenia. Nat. Genet. 45, 1150–1159 (2013).
33. Wray, N. R. et al. Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression. Nat. Genet. 50, 668–681 (2018).
34. Okbay, A. et al. Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses. Nat. Genet. 48, 624–633 (2016).
35. Cross-Disorder Group of the Psychiatric Genomics Consortium et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat. Genet. 45, 984–994 (2013).
36. Duncan, L. et al. Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. Am. J. Psychiatry 174, 850–858 (2017).
37. Otowa, T. et al. Meta-analysis of genome-wide association studies of anxiety disorders. Mol. Psychiatry 21, 1391–1399 (2016).
38. Gale, C. R. et al. Pleiotropy between neuroticism and physical and mental health: findings from 108 038 men and women in UK Biobank. Transl. Psychiatry 6, e791 (2016).
39. Rietveld, C. A. et al. GWAS of 126,559 individuals identifies genetic variants associated with educational attainment. Science 340, 1467–1471 (2013).
40. Okbay, A. et al. Genome-wide association study identifies 74 loci associated with educational attainment. Nature 533, 539–542 (2016).
41. Benyamin, B. et al. Childhood intelligence is heritable, highly polygenic and associated with FNBP1L. Mol. Psychiatry 19, 253–258 (2014).
42. Sniekers, S. et al. Genome-wide association meta-analysis of 78,308 individuals identifies new loci and genes influencing human intelligence. Nat. Genet. 49, 1107–1112 (2017).
43. MacArthur, J. et al. The new NHGRI-EBI catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 45, D896–D901 (2017).
44. Ikeda, M. et al. A genome-wide association study identifies two novel susceptibility loci and trans population polygenicity associated with bipolar disorder. Mol. Psychiatry 23, 639–647 (2018).
45. Finucane, H. K. et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet. 47, 1228–1235 (2015).
46. Pers, T. H. et al. Biological interpretation of genome-wide association studies using predicted gene functions. Nat. Commun. 6, 5890 (2015).
47. Zhu, Z. et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat. Genet. 48, 481–487 (2016).
48. Pavlides, J. M. W. et al. Predicting gene targets from integrative analyses of summary data from GWAS and eQTL studies for 28 human complex traits. Genome Med. 8, 84 (2016).
49. Qi, T. et al. Identifying gene targets for brain-related traits using transcriptomic and methylomic data from blood. Nat. Commun. 9, 2282 (2018).
50. de Leeuw, C. A., Mooij, J. M., Heskes, T. & Posthuma, D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput. Biol. 11, e1004219 (2015).
51. Bipolar Disorder and Schizophrenia Working Group of the Psychiatric Genomics Consortium. Genomic dissection of bipolar disorder and schizophrenia, including 28 subphenotypes. Cell 173, 1705–1715.e16 (2018).
52. Lee, S. H., Goddard, M. E., Wray, N. R. & Visscher, P. M. A better coefficient of determination for genetic profile analysis. Genet. Epidemiol. 36, 214–224 (2012).
53. Simonsen, C. et al. Neurocognitive dysfunction in bipolar and schizophrenia spectrum disorders depends on history of psychosis rather than diagnostic group. Schizophr. Bull. 37, 73–83 (2011).
54. Goes, F. S. et al. Genome-wide association of mood-incongruent psychotic bipolar disorder. Transl. Psychiatry 2, e180 (2012).
55. Allardyce, J. et al. Association between schizophrenia-related polygenic liability and the occurrence and level of mood-incongruent psychotic symptoms in bipolar disorder. JAMA Psychiatry 75, 28–35 (2018).
56. Palmer, C. & Pe’er, I. Statistical correction of the winner’s curse explains replication variability in quantitative trait genome-wide association studies. PLoS Genet. 13, e1006916 (2017).
57. Goes, F. S. et al. Genome-wide association study of schizophrenia in Ashkenazi Jews. Am. J. Med. Genet. B 168, 649–659 (2015).
58. Gaspar, H. A. & Breen, G. Drug enrichment and discovery from schizophrenia genome-wide association results: an analysis and visualisation approach. Sci. Rep. 7, 12460 (2017).
59. Camandola, S. & Mattson, M. P. Aberrant subcellular neuronal calcium regulation in aging and alzheimer’s disease. Biochim. Biophys. Acta Mol. Cell Res. 1813, 965–973 (2011).
60. Mertens, J. et al. Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature 527, 95–99 (2015).
61. Yang, C.-P. et al. Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes. Nat. Commun. 9, 838 (2018).
62. Lee, S.-H., Zabolotny, J. M., Huang, H., Lee, H. & Kim, Y.-B. Insulin in the nervous system and the mind: functions in metabolism, memory, and mood. Mol. Metab. 5, 589–601 (2016).
63. McIntyre, R. S. et al. A randomized, double-blind, controlled trial evaluating the effect of intranasal insulin on neurocognitive function in euthymic patients with bipolar disorder. Bipolar Disord. 14, 697–706 (2012).
64. Desfossés, J., Stip, E., Bentaleb, L. A. & Potvin, S. Endocannabinoids and schizophrenia. Pharmaceuticals 3, 3101–3126 (2010).
65. Zamberletti, E., Rubino, T. & Parolaro, D. The endocannabinoid system and schizophrenia: integration of evidence. Curr. Pharm. Des. 18, 4980–4990 (2012).
66. Serra, G. & Fratta, W. A possible role for the endocannabinoid system in the neurobiology of depression. Clin. Pract. Epidemiol. Ment. Health 3, 25 (2007).
67. MacCabe, J. H. et al. Excellent school performance at age 16 and risk of adult bipolar disorder: national cohort study. Br. J. Psychiatry 196, 109–115 (2010).
68. Vreeker, A. et al. High educational performance is a distinctive feature of bipolar disorder: a study on cognition in bipolar disorder, schizophrenia patients, relatives and controls. Psychol. Med. 46, 807–818 (2016).
69. Ripke, S. Ricopili: a Tool for Visualizing Regions of Interest in Select GWAS Data Sets (Broad Institute, 2014).
70. Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).
71. Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).
72. Euesden, J., Lewis, C. M. & O’Reilly, P. F. PRSice: Polygenic Risk Score software. Bioinformatics 31, 1466–1468 (2015).
73. Finucane, H. et al. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat. Genet. 50, 621–629 (2018).
74. O’Dushlaine, C. et al. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nat. Neurosci. 18, 199–209 (2015).
75. 1000 Genomes Project Consortium et al. A global reference for human genetic variation. Nature 526, 68–74 (2015).
76. Olier, I., Vellido, A. & Giraldo, J. Kernel generative topographic mapping. In Proc. 18th European Symposium on Artificial Neural Networks (ed. Verleysen, M.) 481–486 (ESANN, 2010).