An exploration of the genetic epidemiology of non-suicidal self-harm and suicide attempt.

BACKGROUND: Empirical evidence supporting the distinction between suicide attempt (SA) and non-suicidal self-harm (NSSH) is lacking. Although NSSH is a risk factor for SA, we do not currently know whether these behaviours lie on a continuum of severity, or whether they are discrete outcomes with different aetiologies. We conducted this exploratory genetic epidemiology study to investigate this issue further. METHODS: We explored the extent of genetic overlap between NSSH and SA in a large, richly-phenotyped cohort (the Avon Longitudinal Study of Parents and Children; N = 4959), utilising individual-level genetic and phenotypic data to conduct analyses of genome-wide complex traits and polygenic risk scores (PRS). RESULTS: The single nucleotide polymorphism heritability of NSSH was estimated to be 13% (SE 0.07) and that of SA to be 0% (SE 0.07). Of the traits investigated, NSSH was most strongly correlated with higher IQ (rG = 0.31, SE = 0.22), there was little evidence of high genetic correlation between NSSH and SA (rG = - 0.1, SE = 0.54), likely due to the low heritability estimate for SA. The PRS for depression differentiated between those with NSSH and SA in multinomial regression. The optimal PRS prediction model for SA (Nagelkerke R2 0.022, p < 0.001) included ADHD, depression, income, anorexia and neuroticism and explained more variance than the optimal prediction model for NSSH (Nagelkerke R2 0.010, p < 0.001) which included ADHD, alcohol consumption, autism spectrum conditions, depression, IQ, neuroticism and suicide attempt. CONCLUSIONS: Our findings suggest that SA does not have a large genetic component, and that although NSSH and SA are not discrete outcomes there appears to be little genetic overlap between the two. The relatively small sample size and resulting low heritability estimate for SA was a limitation of the study. Combined with low heritability estimates, this implies that family or population structures in SA GWASs may contribute to signals detected