The promise of disease gene discovery in South Asia

Abstract

It is tempting to think of the more than 1.5 billion people who live in South Asia as one large ethnic group, but in fact, South Asia is better viewed as comprised of very many small endogamous groups that usually marry within their own group (caste or tribe). To perform a high resolution assessment of South Asian demography, we assembled genome-wide data from over 2,000 individuals from over 250 distinct South Asian groups, more than tripling the number of diverse India groups for which such data are available, and including tribe and caste groups sampled from every state in India. We document shared ancestry across groups that correlates with geography, language, and caste affiliation, and characterize the strength of the founder events that gave rise to many of these groups. Over a third of the groups, including eighteen with census sizes of more than a million, descend from founder events stronger than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to their histories of strong founder events. These results highlight a major and unappreciated opportunity for reducing the disease burden among South Asians through the discovery of and genetic testing for recessive disease genes.