Establishing the Suicide Working Group of the Psychiatric Genomics Consortium to elucidate the genetics and biology of suicide outcomes

PROJECT SUMMARY Suicide results in 130 preventable American deaths every day, and >700,000 deaths worldwide each year. Non- fatal suicide attempt (SA) affects an even larger proportion of the population with estimates 10-25 times the number of individuals who die by suicide (1.4 million in the US, >20 million worldwide). Suicidal ideation (SI), the contemplation of taking one’s own life, is even more common, with a cross-national lifetime prevalence of 9.2%. While these suicide outcomes are all significantly heritable, only recently have samples reached sufficient size to conduct well-powered genetic studies, and thus far, these have largely been limited to SA. Large-scale genetic studies of the full spectrum of suicide outcomes are necessary to elucidate their genetic and biological etiologies, potential drug targets, and the similarities and differences between them. Here, we establish the Suicide Working Group of the Psychiatric Genomics Consortium, to interrogate the biological basis of the full spectrum of suicide outcomes in individuals of diverse ancestries, leveraging clinical, population, and medical examiner resources worldwide. This project will characterize the genetic etiology of suicide outcomes through genome-wide association studies of at least 69,800 SA cases, 19,500 suicide death (SD) cases, and 206,900 SI cases. We will elucidate the shared and distinct genetic etiology between suicide outcomes and psychiatric disorders, and between SA, SD and SI, illuminating the similarities and differences between them. These results will be used to identify biologically relevant tissues, cell-types, pathways, and drug targets, and to prioritize causal genes and SNPs underlying genome-wide significant loci. Overall, this proposal dramatically expands and diversifies efforts to understand the etiology of suicide outcomes, combining prior efforts and expertise from the PI and Co-Is in genomic studies of SA, SD and SI. The study will provide novel biological insights into genetic risk of suicide outcomes that will enable potential avenues of therapeutic understanding and risk stratification. Finally, it will facilitate the worldwide collaborative growth of a highly-powered cohort of diverse ancestries, environmental exposures, and phenotypes, in which to address many future questions related to suicide outcomes.