BUILDING RESOURCES FOR THE DIVERSIFICATION OF GENOMIC DATA ON SUICIDE MORTALITY

Abstract

To date, a lack of population-based genetic data from under-represented populations continues to limit the impact and global generalizability of large-scale genetic and epidemiological studies of suicide mortality. India represents the majority of global suicide deaths: 36.6% of global suicide deaths among females, and 24.3% among males. Moreover, the suicide rate among girls and women in India is twice the global rate. In addition to genetic risk factors, there are myriad unique cultural and environmental factors that are expected to 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 these regions will be critical for designing new prevention initiatives and reducing global suicide rates. Professor Chittaranjan Behera M.D., of the All-India Institute for Medical Sciences in Delhi, will present a collaborative study, supported by the Fogarty International Center and the National Institutes of Health, to facilitate the collection of blood, brain tissue, phenotypic and toxicology information, and psychological autopsy data in Delhi, India. Collection is currently underway and will include 4,000 population-based postmortem suicide deaths and postmortem controls, with collection brain tissue from half of this cohort. This study is intended to develop a lasting, impactful global research resource in India, with partnership between the All-India Institute for Medical Sciences in Delhi and the University of Utah School of Medicine. This study currently represents the first collection of non-European suicide postmortem blood and brain tissue in the world, and it is hoped that this new comparison population will significantly impact our current models of suicide risk. For example, for the first time, top loci in large genetic analyses of suicide can be studied across ancestral populations and can be validated in secondary analyses of differential gene expression in postmortem brain. Polygenic profiling of population-based suicide has also informed our understanding of suicide mortality in the U.S., where a majority of individuals who die lack any mental health diagnoses or other medical records, and where these individuals typically differ both demographically and clinically from people who attempt suicide but do not die. Pilot genetic data examined by the research team suggest 1) that GWAS summary data from this study will significantly improve the generalizability and out-of-sample polygenic prediction of global GWAS meta-analyses, 2) that there is some portability of polygenic prediction of suicide phenotypes across Indian and European ancestry admixtures, and 3) that polygenic profiling of comparative risks in an Indian population is possible. With this close research partnership, we hope to gain a valuable and representative comparison cohort with which to better understand suicide risks, and to lay the groundwork for future clinical and genomic studies of postmortem suicide. Additionally, capacity building efforts have allowed the research teams in India and the U.S. to train one another in best practices, to begin to study cultural differences relevant to suicide risk and suicide prevention, to practice equitable collaboration, and to develop the expertise and professional careers of individuals intending to remain in Delhi and train future researchers.