Genetic aetiology of self-harm ideation and behaviour

Adrian I Campos,Ann John,Katrina A S Davis,Dominique F Maciejewski,Miguel E Rentería,Dixie J Statham,Nicholas G Martin,Pamela A F Madden,Andrew C Heath,Karin J H Verweij,Matthew Hotopf

doi:10.1038/s41598-020-66737-9

Abstract

Family studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. However, the genetic aetiology of broad sense (non-suicidal and suicidal) self-harm has not been characterised on the molecular level. In addition, controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. In the present study, we conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). We also perform genome wide gene-based tests and characterize the SNP heritability and genetic correlations between these traits. Finally, we test whether polygenic risk scores (PRS) for self-harm ideation and self-harm behaviour predict suicide attempt, suicide thoughts and non-suicidal self-harm (NSSH) in an independent target sample of 8,703 Australian adults. Our GWAS results identified one genome-wide significant locus associated with each of the two phenotypes. SNP heritability (hsnp2) estimates were ~10%, and both traits were highly genetically correlated (LDSC rg > 0.8). Gene-based tests identified seven genes associated with self-harm ideation and four with self-harm behaviour. Furthermore, in the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. Evidence for shared genetic aetiology between NSSH and suicide attempt was not statistically significant.

Highlights

Studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders
We explore the genetic aetiology of lifetime self-harm ideation and lifetime self-harm behaviour using a genome-wide association studies (GWAS) and polygenic risk scores (PRS) approach
In the discovery sample, where genetic correlates of broad sense self-harm ideation and self-harm behaviour were assessed, males and females presented a similar age range, but females showed a higher prevalence of both self-harm ideation and self-harm www.nature.com/scientificreports

Summary

Introduction

Studies have identified a heritable component to self-harm that is partially independent from comorbid psychiatric disorders. Controversy exists about the degree to which suicidal and non-suicidal self-harm share a common genetic aetiology. We conduct genome-wide association studies (GWAS) on lifetime self-harm ideation and self-harm behaviour (i.e. any lifetime self-harm act regardless of suicidal intent) using data from the UK Biobank (n > 156,000). In the target sample, PRS for self-harm ideation were significantly associated with suicide thoughts and NSSH, and PRS for self-harm behaviour predicted suicide thoughts and suicide attempt. Follow up regressions identified a shared genetic aetiology between NSSH and suicide thoughts, and between suicide thoughts and suicide attempt. We explore the genetic aetiology of lifetime self-harm ideation and lifetime self-harm behaviour (regardless of suicidal intent) using a GWAS and PRS approach.

Methods

Results

Conclusion