Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study
Molecular studies have attempted to identify specific genes that contribute to suicide risk and mental disorders are strongly linked to suicidal behavior. Given that liability for a wide range of mental disorders is associated with a common set of genetic factors, it is plausible that the effect of genes on suicidal behavior could be mediated through their impact on mental disorders. Although family studies have indicated support for a genetic transmission of suicidal behavior independent of mental disorders this remains to be confirmed using molecular genetic data.
About the study
Using the iPSYCH sample, we set out to examine whether specific genetic variants were associated with suicide attempt using a GWAS approach while controlling for mental disorders. After quality control, a total of 6,024 individuals with suicide attempt and 44,240 controls with no record of a suicide attempt were included in the analysis. The study sample consisted of young adults living in Denmark during 1980-2013.
We found several suggestive associations to suicide attempt in the GWAS adjusted for socio-demographic variables. When adjusting for mental disorders, three significant associations, all on chromosome 20, were identified: rs4809706 (p-value: 2.8 × 10-8), rs4810824 (p-value: 3.5 × 10-8), and rs6019297 (p-value: 4.7 × 10 -8). When comparing individuals with affective disorder and attempted suicide to healthy controls, a novel association in the intronic region of the gene PDE4B was identified. We found that SNP heritability for suicide attempt was 4.6% (CI-95: 2.9–6.3%) when adjusting for sociodemographic characteristics. When also adjusting for mental disorders, the heritability decreased to 1.9% (CI-95: 0.3–3.5%). There was some support for suicide-related behaviours or mental disorders in the identified SNP's with a suggestive or significant association.
Our heritability estimate suggests that diagnosed mental disorders do not fully explain the genetic transmission of a suicide attempt. It is, of course, possible that undiagnosed mental disorder might account for a substantial share of the residual heritability. The heritability estimate can at best provide a lower bound for the actual heritability of suicidal behaviours. We concluded that our study identified novel candidate genes for suicide attempt and that some SNP heritability could be established.
The article Genetics of suicide attempts in individuals with and without mental disorders: a population-based genome-wide association study was published in Molecular Psychiatry, August 2018.
Facts about the study
- The largest GWAS to date to focus on genetic predictors of suicide attempts
- Population-based data allowed us to stratify for mental disorders that are strongly associated with suicidal behaviour.
- Some SNP heritability for suicide attempt could be established.
Annette Erlangsen, Senior Researcher, Mental Health Centre Copenhagen, Capital Region of Denmark, Email: email@example.com