Background/Aims: The pathophysiology of suicidal behaviour is complex and dynamic, arising from an interplay of sociological, biological, environmental, and psychological factors. Although vitamin D is primarily associated with bone health, recent studies have highlighted its involvement in immune responses, cardiovascular function, and brain health. This research aims to explore the genetic components of both traits on a population scale and identify potential shared genetic architecture. Genome-wide association study (GWAS) summary statistics for suicide attempt and vitamin D from previously published studies were analysed. Linkage disequilibrium score regression was used to estimate single nucleotide polymorphism (SNP)-based heritability and genome-wide genetic correlations to assess overall shared genetic regulation. Conditional false discovery rate (cFDR) methods were employed to identify shared genomic regions by considering the traits together. Additionally, conjunctional cFDR was used to assess genetic loci independently associated with both traits. SNP-based heritability estimates for suicide attempt and serum vitamin D levels were 6.9% (s.e. = 0.017, p<0.025) and 7% (s.e. = 0.006, p<0.025) on the liability scale. Genetic correlations of -0.14 (s.e. = 0.06, p<0.025) was observed between these traits. Conjunctional cFDR analysis identified a shared locus between the two traits in the European population on chromosome 11.

Conclusions: This study identified a negative genetic correlation between suicide attempts and serum vitamin D levels, with shared locus on chromosome 11. This locus maps to the RRAS2 gene, which plays a key role in neuroinflammatory pathways. The findings suggest neuroinflammation as a potential mechanistic link between suicidal behaviour and vitamin D that requires further investigation.