0031 Shared Genetic Mechanisms Underlying Association Between Sleep Disturbances and Depressive Symptoms

Abstract Introduction Although associations between insomnia and major depression disorder have been reported, little is known about the shared genetic mechanisms underlying their comorbidity. Polygenic scores (PGS) for sleep disturbances and depressive symptoms in an epidemiological cohort were calculated and correlated. Genes assigned to variants that compose the best-fit PGS predictions were overlapped to explore the shared genetic bases of sleep problems and depressive symptoms. Methods Human OmniExpress BeadChip genotyping was performed on the São Paulo Epidemiologic Sleep Study (EPISONO, N=1042), an adult epidemiological sample subjected to a sleep-based survey. PGS analysis was performed on 900 individuals with PRSice2. Summary statistics from a genome wide association study (GWAS) for depression (N=500,199, United Kingdom Biobank (UKBB) and Psychiatry Genetics Consortium) grounded the PGS calculations for Beck Depression Index (BDI), while insomnia GWAS (N=386,988, UKBB) based the PGS for Insomnia Severity Index (ISI) and Pittsburg Sleep Quality Index (PSQI) in EPISONO. Pearson’s correlation was applied to contrast PGS and clinical scores. Genes were assigned to SNPs using Ensembl Variant Effect Predictor and Fisher’s Exact test was used to test the overlap between gene lists. Pathway enrichment analysis was performed on sets of interest genes using Benjamin-Hochberg test. Results All PGS models were significant when individuals were divided as cases or controls according to BDI, PSQI and ISI scales. When clinical scales were used as continuous variables, the best-fit PGS models for BDI (p=0.0004, R2=1.56%) and PSQI scores (p=0.0058, R2=0.87%) reached statistical significance, but PGS calculations were unable to significantly predict ISI scores. PSQI and BDI scores were highly correlated, and the same observation was applied to PGS for sleep quality and depressive symptoms. Genes associated with the variants which compose the best-fit PGS predictions for sleep quality and depressive symptoms were significantly overlapped. Pathways enriched among the intersect genes are related to synapse function and formation. Conclusion The genetic bases of sleep quality and depressive symptoms are correlated; their implicated genes are significantly overlapped and converge on neural pathways. This data suggests that sleep complaints accompanying depressive symptoms are not secondary issues, but part of the core mental illness. Support (if any) AFIP, FAPESP, CNPq.