T89. ASSESSING THE GENETIC AND ENVIRONMENTAL INTERPLAY BETWEEN VITAMIN D STATUS AND SUICIDAL BEHAVIOUR

Suicidal ideation and behaviour have complex pathophysiology, stemming from multifactorial origins including biological, sociological, environmental, and psychological factors. Despite the growing identification of risk factors, including genetic variants, understanding of the underlying mechanisms or biomarkers across the suicidal behaviour spectrum remains limited. Vitamin D (VitD) is influential on both immune and neurological systems, and its role is under investigation in various neurological and psychiatric disorders. VitD deficiency has become more prevalent globally, especially in higher-latitude countries. VitD has been implicated in suicidal biology, though evidence remains scarce and inconclusive. Our research aims to evaluate whether VitD is associated with suicidal behaviour, and whether it might represent a modifiable biological factor. Participants with valid serum 25-hydroxyvitamin D [25(OH)D] data (n = 445,889), and those with mental health questionnaire data (n = 155,883) or intentional self-harm listed as primary cause of death (ICD codes X60-X84, n = 306) were included from the UK Biobank (UKB) cohort. Suicidal behaviour was defined by the most severe of the non-overlapping categories: none, thoughts that life not worth living, self-harm/suicidal ideation, self-harm behaviour, suicide attempt, and suicide death. VitD status was categorised as deficient where serum levels were < 25nmol/L or marked below assay detection (< 10nmol/L). Genome-wide association summary statistics for suicidal ideation, suicide attempt, and VitD (serum 25(OH)D) will be analysed using data from Docherty et al (2023), Ashley-Koch et al (2023), Jiang et al (2018) and Albiñana et al (2023). Linkage disequilibrium score regression (LDSC) will be used to estimate SNP -based heritabilities (h2SNP) and genetic correlations. Conditional false discovery rate (cFDR) methods will identify shared genomic regions. Bidirectional effects of polygenic risk scores for suicidal behaviour and VitD levels will be assessed, incorporating a range of biological and sociodemographic factors from the UKB. Preliminary multinomial logistic regression indicated that VitD deficiency was more prevalent in the individuals with lifetime occurrence of thoughts that life was not worth living, suicidal ideation, self-harm and attempted suicide (relative risk ratio [95%CI]: 1.16 [1.05-1.28], 1.25 [1.11-1.41], 1.39 [1.10-1.75] and 1.62 [1.30-2.02], p < 0.0125, respectively) compared to no suicidality. VitD deficiency and suicide death was found not to be significantly associated (3.73 [0.59-23.49], p=0.16), possibly due to a relatively small sample size. LDSC of suicide attempt and serum vitamin D levels h2SNP were estimated to be 5.6% (s.e=0.004, p < 2.26 × 10 −54) and 7% (s.e.=0.018, p < 1.39 × 10−4) on a liability scale, with genetic correlation of -0.13 (se=0.063, p < 0.05). The conjunction cFDR analysis identified two shared SNPs between the two traits in the EUR population, with further analysis planned for other ancestry groups. Preliminary results suggest that individuals with suicidal ideation and/or behaviour are more likely to have lower serum VitD levels. Exploring this association using genetics will enable the assessment of shared biology, potential causality, interactions with other factors, and the potential of VitD as a biomarker or modifiable risk factor that could inform future suicide prevention strategies.