Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study

• Published in: Molecular psychiatry Vol. 25; no. 10; pp. 2410 - 2421
• Main Authors: Erlangsen, Annette, Appadurai, Vivek, Wang, Yunpeng, Turecki, Gustavo, Mors, Ole, Werge, Thomas, Mortensen, Preben B, Starnawska, Anna, Børglum, Anders D, Schork, Andrew, Nudel, Ron, Bækvad-Hansen, Marie, Bybjerg-Grauholm, Jonas, Hougaard, David M, Thompson, Wesley K, Nordentoft, Merete, Agerbo, Esben
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.10.2020; Nature Publishing Group UK
• Subjects: Adolescent; Adult; Affective disorders; Aggregation behavior; Analysis; Autism; Chromosome 20; Chromosomes; Cohort Studies; Demography; Domestic relations; Family studies; Female; Genetic aspects; Genome-wide association studies; Genome-Wide Association Study; Genomes; Genomics; Health aspects; Heritability; Humans; Male; Mental disorders; Mental Disorders - genetics; Mental Disorders - psychology; Mood Disorders - genetics; Mood Disorders - psychology; Pervasive developmental disorders; Population studies; Population-based studies; Quality control; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Suicidal behavior; Suicidal Ideation; Suicide; Suicide, Attempted; Suicides & suicide attempts; Young Adult
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-018-0218-y

Family studies have shown an aggregation of suicidal behavior in families. Yet, molecular studies are needed to identify loci accounting for genetic heritability. We conducted a genome-wide association study and estimated single nucleotide polymorphisms (SNP) heritability for a suicide attempt. In a case-cohort study, national data on all individuals born in Denmark after 1981 and diagnosed with severe mental disorders prior to 2013 (n = 57,377) and individuals from the general population (n = 30,000) were obtained. After quality control, the sample consisted of 6024 cases with an incidence of suicide attempt and 44,240 controls with no record of a suicide attempt. Suggestive associations between SNPs, rs6880062 (p-value: 5.4 × 10 ) and rs6880461 (p-value: 9.5 × 10 ), and suicide attempt were identified when adjusting for socio-demographics. Adjusting for mental disorders, three significant associations, all on chromosome 20, were identified: rs4809706 (p-value: 2.8 × 10 ), rs4810824 (p-value: 3.5 × 10 ), and rs6019297 (p-value: 4.7 × 10 ). Sub-group analysis of cases with affective disorders revealed SNPs associated with suicide attempts when compared to the general population for gene PDE4B. All SNPs explained 4.6% [CI-95: 2.9-6.3%] of the variation in suicide attempt. Controlling for mental disorders reduced the heritability to 1.9% [CI-95: 0.3-3.5%]. Affective and autism spectrum disorders exhibited a SNP heritability of 5.6% [CI-95: 1.9-9.3%] and 9.6% [CI-95: 1.1-18.1%], respectively. Using the largest sample to date, we identified significant SNP associations with suicide attempts and support for a genetic transmission of suicide attempt, which might not solely be explained by mental disorders.