ADVANCING THE GENOMICS OF SUICIDALITY: NEW FINDINGS FROM THE SUICIDE WORKING GROUP OF THE PSYCHIATRIC GENOMICS CONSORTIUM

Overall Abstract Over 700,000 preventable suicide deaths (SDs) occur annually, and non-fatal suicide attempts (SAs) and suicidal ideation (SI) are vastly more common. Despite their substantial public health impact, the etiology of suicidality remains poorly understood, treatment options are lacking, and risk prediction remains elusive. The heritability of suicidality is established by twin and family studies at 30-55% and known to be partially distinct from that of psychiatric disorders. In this symposium, we showcase recent highlights in suicide genomics research, covering the spectrum of suicidality, common and rare genetic variation, and novel biological insights. The first talk by Sarah Colbert, BA will describe multivariate genome-wide association studies (GWAS) by the Psychiatric Genomics Consortium (PGC) which dissect the shared and distinct genetic architectures of SI, SA, and SD, and clarify their relationships with each other and psychiatric disorders. The second talk by Anna Docherty, PhD will present PGC sex-specific GWAS of SI cases (14,153 male, 29,196 female), SA cases (8,291 male, 18,636 female) and SD cases (5,299 male, 1,510 female), addressing longstanding questions about sex differences and incorporating post-GWAS analyses to identify relevant biological pathways, tissues and cell-types. The third presentation by Barbara Šakić, MSc will share results from the first well-powered study identifying drug targets and drug repurposing opportunities for suicidality leveraging genetic methods and molecular analyses to identify potential therapeutically actionable pathways. The final talk by Alexander Hatoum, PhD will address genetic heterogeneity and the limited predictive performance of polygenic risk scores (PRS) by applying multi-annotated polygenic risk prediction and gradient tree-based machine learning methods to improve genetic risk prediction and stratification. Together, these presentations span a diverse set of methods, including genomic structural equation modeling, GWAS, drug enrichment analyses, and polygenic risk scoring, bridging fundamental genetic analyses and translational application. The symposium also reflects diversity in expertise and perspective, with the presenters, co-chairs, and discussants spanning different career stages (2 PhD students and 4 faculty), five different institutions, and varied education and research backgrounds in statistical genetics, clinical psychology, and translational genomics.