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The more than 1.5 billion people who live in South Asia are correctly viewed not as a single large population, but as many small endogamous groups. We assembled genome-wide data from over 2,800 individuals from over 260 distinct South Asian groups. We identify 81 unique groups, of which 14 have estimated census sizes of more than a million, that descend from founder events more extreme than those in Ashkenazi Jews and Finns, both of which have high rates of recessive disease due to founder events. We identify multiple examples of recessive diseases in South Asia that are the result of such founder events. This study highlights an under-appreciated opportunity for reducing disease burden among South Asians through the discovery of and testing for recessive disease genes.

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