Building Resources for the Diversification of Genetic Data on Suicide Death

PROJECT SUMMARY Suicide results in >800,000 world deaths and >40,000 U.S. deaths annually. Suicide rates in India, rising over the past five decades, now reflect the highest rates in the world. India's contribution to global suicide deaths increased from 25.3% in 1990 to 36.6% in 2016 among women, and from 18.7% to 24.3% among men. Moreover, the suicide rate among girls and women in India continues to be twice the global rate. Yet while several environmental and genetic risk factors for suicide have been identified globally, India remains completely unrepresented in global research efforts. More broadly, a lack of population-based data from under- represented populations greatly limits the impact and global generalizability of genetic and epidemiological studies of suicide death. There are, in particular, myriad cultural and environmental factors that are expected to dynamically influence risk for suicide in low- to middle-income countries (LMICs). Four in five suicides in young people (<30 years) globally occur in LMICs, and a better understanding of suicide in LMICs will be critical for designing stigma reduction initiatives and informing prevention efforts. Genetic analysis of population-based suicide death in Utah has dramatically informed models of risk in the U.S., where a majority of deaths lack psychiatric or other medical records, but have been profiled for hundreds of polygenic risks. This project aims to 1) collect blood, phenotypic information, psychological autopsy, and toxicology data from 4,000 suicide deaths and postmortem controls in Delhi, India, 2) to collect brain tissue from multiple areas of the brain in half of the suicide deaths and controls (n = 2,000), 3) to genotype all blood samples, and 4) to conduct multiple cross-ancestry analyses of genetic and phenotypic risks, as well as the first (preliminary) genome-wide association study (GWAS) of population-based suicide death in a non-European ancestry population. Genetic data from India will be integrated with U.S. data, meta-analyzed with the U.S. suicide death GWAS, and meta-analyzed with 22 international suicide attempt GWAS from the Psychiatric Genomics Consortium (PGC). Brain samples will be preserved at the All-India Institute for Medical Sciences in Delhi, for future methylation and sequencing analysis with teams across India and the U.S. This biosample collection will represent the only other resource for population-based suicide death in the world, after Utah, and as a diverse ancestry cohort with psychological autopsy, blood, and brain tissue, it stands to significantly impact global suicide research.