Nat Genet. 2017 Sep;49(9):1403-1407. doi: 10.1038/ng.3917. Epub 2017 Jul 17.

The promise of discovering population-specific disease-associated genes in South Asia.

Nakatsuka N^1,², Moorjani P^3,⁴, Rai N⁵, Sarkar B⁶, Tandon A^1,⁴, Patterson N⁴, Bhavani GS⁷, Girisha KM⁷, Mustak MS⁸, Srinivasan S⁹, Kaushik A¹⁰, Vahab SA¹¹, Jagadeesh SM¹², Satyamoorthy K¹¹, Singh L¹³, Reich D^1,^4,¹⁴, Thangaraj K⁵.

Author information

1: Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
2: Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts, USA.
3: Department of Biological Sciences, Columbia University, New York, New York, USA.
4: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
5: CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India.
6: Anthropological Survey of India, Kolkata, India.
7: Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal, India.
8: Department of Applied Zoology, Mangalore University, Mangalore, India.
9: Centre for Human Genetics, Bangalore, India.
10: Amity Institute of Biotechnology, Amity University, Noida, India.
11: School of Life Sciences, Manipal University, Manipal, India.
12: Fetal Care Research Foundation, Chennai, India.
13: Genome Foundation, Hyderabad, India.
14: Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

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 identified 81 unique groups, 14 of which had estimated census sizes of more than 1 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 identified multiple examples of recessive diseases in South Asia that are the result of such founder events. This study highlights an underappreciated opportunity for decreasing disease burden among South Asians through discovery of and testing for recessive disease-associated genes.