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


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.

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Figure 1: Data set overview.
Figure 2: Example histograms of IBD segments, illustrating the differences between groups with founder events of different magnitudes.
Figure 3: IBD scores relative to Finns (FIN).


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We are thankful to the many Indian, Pakistani, Bangladeshi, Sri Lankan, and Nepalese individuals who contributed the DNA samples analyzed here, including the patients with PPD and MPS IVA. We are grateful to A. Basu and P. P. Majumder (National Institute of Biomedical Genomics, Kalyani, India) for early sharing of data. Funding was provided by an NIGMS (GM007753) fellowship to N.N.; a Translational Seed Fund grant from the Dean's Office of Harvard Medical School, and grant HG006399 to D.R.; a Council of Scientific and Industrial Research, Government of India grant to K.T.; support from TIFAC-CORE to S.A.V. and K.S.; and NIGMS grant 115006 to P.M. The study of MPS IVA patients was funded by grants from the Department of Biotechnology, Government of India (BT/PR4224/MED/97/60/2011 to S.S. and S.M.J.) and the Department of Science and Technology, Government of India (SR/WOS-A/LS-83/2011 to S.S.). Funding for the mutation analysis of Indian patients with PPD was provided by the Indian Council of Medical Research (BMS 54/2/2013) to K.M.G. D.R. is supported as an Investigator of the Howard Hughes Medical Institute.

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Authors and Affiliations



N.N., P.M., D.R., and K.T. conceived the study. N.N., P.M., N.R., B.S., A.T., N.P., and D.R. performed analysis. G.S.B., K.M.G., M.S.M., S.S., A.K., S.A.V., S.M.J., K.S., L.S., and K.T. collected data. N.N., D.R., and K.T. wrote the manuscript with the help of all coauthors.

Corresponding authors

Correspondence to David Reich or Kumarasamy Thangaraj.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6, Supplementary Tables 1–4 and 6, and Supplementary Note. (PDF 8052 kb)

Supplementary Table 5

IBD, FST, and group-specific drift analyses. (XLSX 114 kb)

Life Sciences Reporting Summary (PDF 134 kb)

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Nakatsuka, N., Moorjani, P., Rai, N. et al. The promise of discovering population-specific disease-associated genes in South Asia. Nat Genet 49, 1403–1407 (2017).

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