title: Genetic relationships between suicide attempts, suicidal ideation and major psychiatric disorders: a genome-wide association and polygenic scoring study.
abstract: Epidemiological studies have recognized a genetic diathesis for suicidal behavior, which is independent of other psychiatric disorders. Genome-wide association studies (GWAS) on suicide attempt (SA) and ideation have failed to identify specific genetic variants. Here, we conduct further GWAS and for the first time, use polygenic score analysis in cohorts of patients with mood disorders, to test for common genetic variants for mood disorders and suicide phenotypes. Genome-wide studies for SA were conducted in the RADIANT and GSK-Munich recurrent depression samples and London Bipolar Affective Disorder Case-Control Study (BACCs) then meta-analysis was performed. A GWAS on suicidal ideation during antidepressant treatment had previously been conducted in the Genome Based Therapeutic Drugs for Depression (GENDEP) study. We derived polygenic scores from each sample and tested their ability to predict SA in the mood disorder cohorts or ideation status in the GENDEP study. Polygenic scores for major depressive disorder, bipolar disorder and schizophrenia from the Psychiatric Genomics Consortium were used to investigate pleiotropy between psychiatric disorders and suicide phenotypes. No significant evidence for association was detected at any SNP in GWAS or meta-analysis. Polygenic scores for major depressive disorder significantly predicted suicidal ideation in the GENDEP pharmacogenetics study and also predicted SA in a combined validation dataset. Polygenic scores for SA showed no predictive ability for suicidal ideation. Polygenic score analysis suggests pleiotropy between psychiatric disorders and suicidal ideation whereas the tendency to act on such thoughts may have a partially independent genetic diathesis.
authors: MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, United Kingdom.
authors: Niamh
authors: N
authors: Mullins
authors: Nader
authors: N
authors: Perroud
authors: Rudolf
authors: R
authors: Uher
authors: Amy W
authors: AW
authors: Butler
authors: Sarah
authors: S
authors: Cohen-Woods
authors: Margarita
authors: M
authors: Rivera
authors: Karim
authors: K
authors: Malki
authors: Jack
authors: J
authors: Euesden
authors: Robert A
authors: RA
authors: Power
authors: Katherine E
authors: KE
authors: Tansey
authors: Lisa
authors: L
authors: Jones
authors: Ian
authors: I
authors: Jones
authors: Nick
authors: N
authors: Craddock
authors: Michael J
authors: MJ
authors: Owen
authors: Ania
authors: A
authors: Korszun
authors: Michael
authors: M
authors: Gill
authors: Ole
authors: O
authors: Mors
authors: Martin
authors: M
authors: Preisig
authors: Wolfgang
authors: W
authors: Maier
authors: Marcella
authors: M
authors: Rietschel
authors: John P
authors: JP
authors: Rice
authors: Bertram
authors: B
authors: Müller-Myhsok
authors: Elisabeth B
authors: EB
authors: Binder
authors: Susanne
authors: S
authors: Lucae
authors: Marcus
authors: M
authors: Ising
authors: Ian W
authors: IW
authors: Craig
authors: Anne E
authors: AE
authors: Farmer
authors: Peter
authors: P
authors: McGuffin
authors: Gerome
authors: G
authors: Breen
authors: Cathryn M
authors: CM
authors: Lewis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D003863:Depression / Q000235:genetics; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D059020:Suicidal Ideation; D013406:Suicide, Attempted; D055815:Young Adult
keywords: association; meta-analysis; pleiotropy; prediction