학술논문

GWAS of Suicide Attempt in Psychiatric Disorders and Association With Major Depression Polygenic Risk Scores
Document Type
article
Author
Mullins, NiamhBigdeli, Tim BBørglum, Anders DColeman, Jonathan RIDemontis, DitteMehta, DivyaPower, Robert ARipke, StephanStahl, Eli AStarnawska, AnnaAnjorin, AdebayoCorvin, AidenSanders, Alan RForstner, Andreas JReif, AndreasKoller, Anna CŚwiątkowska, BeataBaune, Bernhard TMüller-Myhsok, BertramPenninx, Brenda WJHPato, CarlosZai, ClementRujescu, DanHougaard, David MQuested, DigbyLevinson, Douglas FBinder, Elisabeth BByrne, Enda MAgerbo, EsbenStreit, FabianMayoral, FerminBellivier, FrankDegenhardt, FranziskaBreen, GeromeMorken, GunnarTurecki, GustavoRouleau, Guy AGrabe, Hans JVölzke, HenryJones, IanGiegling, InaAgartz, IngridMelle, IngridLawrence, JacobWalters, James TRStrohmaier, JanaShi, JianxinHauser, JoannaBiernacka, Joanna MVincent, John BKelsoe, JohnStrauss, John SLissowska, JolantaPimm, JonathanSmoller, Jordan WGuzman-Parra, JoséBerger, KlausScott, Laura JJones, Lisa AAzevedo, M HelenaTrzaskowski, MaciejKogevinas, ManolisRietschel, MarcellaBoks, MarcoIsing, MarcusGrigoroiu-Serbanescu, MariaHamshere, Marian LLeboyer, MarionFrye, MarkNöthen, Markus MAlda, MartinPreisig, MartinNordentoft, MereteBoehnke, MichaelO’Donovan, Michael COwen, Michael JPato, Michele TRenteria, Miguel EBudde, MonikaWeissman, Myrna MWray, Naomi RBass, NicholasCraddock, NicholasSmeland, Olav BAndreassen, Ole AMors, OleGejman, Pablo VSklar, PamelaMcGrath, PatrickHoffmann, PerMcGuffin, PeterLee, Phil HMortensen, Preben BoKahn, René SOphoff, Roel AAdolfsson, RolfVan der Auwera, SandraDjurovic, SrdjanKloiber, StefanHeilmann-Heimbach, Stefanie
Source
American Journal of Psychiatry. 176(8)
Subject
Prevention
Suicide
Serious Mental Illness
Schizophrenia
Human Genome
Depression
Mental Health
Genetics
Brain Disorders
Aetiology
2.3 Psychological
social and economic factors
2.1 Biological and endogenous factors
Mental health
Good Health and Well Being
Bipolar Disorder
Case-Control Studies
Depressive Disorder
Major
Female
Genome-Wide Association Study
Humans
Male
Multifactorial Inheritance
Risk Factors
Suicide
Attempted
M.R.C.Psych
Dr.Med.Sc
Dipl.-Psych
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Bipolar Disorder Working Group of the Psychiatric Genomics Consortium
Schizophrenia Working Group of the Psychiatric Genomics Consortium
Mood Disorders
Polygenic Risk Scoring
Psychiatric Genomics Consortium
Medical and Health Sciences
Psychology and Cognitive Sciences
Psychiatry
Language
Abstract
ObjectiveMore than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium.MethodsThe samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders.ResultsThree genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%).ConclusionsThis study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.