South Asian medical cohorts reveal strong founder effects and high rates of homozygosity

Jeffrey D. Wall (), J. Fah Sathirapongsasuti, Ravi Gupta, Asif Rasheed, Radha Venkatesan, Saurabh Belsare, Ramesh Menon, Sameer Phalke, Anuradha Mittal, John Fang, Deepak Tanneeru, Manjari Deshmukh, Akshi Bassi, Jacqueline Robinson, Ruchi Chaudhary, Sakthivel Murugan, Zameer ul-Asar, Imran Saleem, Unzila Ishtiaq, Areej Fatima, Saqib Shafi Sheikh, Shahid Hameed, Mohammad Ishaq, Syed Zahed Rasheed, Fazal-ur-Rehman Memon, Anjum Jalal, Shahid Abbas, Philippe Frossard, Christian Fuchsberger, Lukas Forer, Sebastian Schoenherr, Qixin Bei, Tushar Bhangale, Jennifer Tom, Santosh Gopi Krishna Gadde, Priya B V, Naveen Kumar Naik, Minxian Wang, Pui-Yan Kwok, Amit V. Khera, B. R. Lakshmi, Adam S. Butterworth, Rajiv Chowdhury, John Danesh, Emanuele Angelantonio, Aliya Naheed, Vinay Goyal, Rukmini M. Kandadai, Hrishikesh Kumar, Rupam Borgohain, Adreesh Mukherjee, Pettarusp M. Wadia, Ravi Yadav, Soaham Desai, Niraj Kumar, Atanu Biswas, Pramod Kumar Pal, Uday B. Muthane, Shymal K. Das, Vedam L. Ramprasad, Prashanth L. Kukkle, Somasekar Seshagiri, Sekar Kathiresan, Arkasubhra Ghosh, V. Mohan, Danish Saleheen, Eric W. Stawiski and Andrew S. Peterson ()
Additional contact information
Jeffrey D. Wall: University of California
J. Fah Sathirapongsasuti: MedGenome Inc.
Ravi Gupta: MedGenome Labs Pvt. Ltd.
Asif Rasheed: Center for Non-Communicable Disease, Karachi
Radha Venkatesan: Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre
Saurabh Belsare: University of California
Ramesh Menon: MedGenome Labs Pvt. Ltd.
Sameer Phalke: MedGenome Labs Pvt. Ltd.
Anuradha Mittal: Thermo Fisher Scientific
John Fang: Thermo Fisher Scientific
Deepak Tanneeru: MedGenome Labs Pvt. Ltd.
Manjari Deshmukh: MedGenome Labs Pvt. Ltd.
Akshi Bassi: MedGenome Labs Pvt. Ltd.
Jacqueline Robinson: University of California
Ruchi Chaudhary: MedGenome Inc.
Sakthivel Murugan: MedGenome Labs Pvt. Ltd.
Zameer ul-Asar: Center for Non-Communicable Disease, Karachi
Imran Saleem: Center for Non-Communicable Disease, Karachi
Unzila Ishtiaq: Center for Non-Communicable Disease, Karachi
Areej Fatima: Center for Non-Communicable Disease, Karachi
Saqib Shafi Sheikh: Punjab Institute of Cardiology
Shahid Hameed: Punjab Institute of Cardiology
Mohammad Ishaq: Karachi Institute of Heart Diseases
Syed Zahed Rasheed: Karachi Institute of Heart Diseases
Fazal-ur-Rehman Memon: Red Crescent Institute of Cardiology
Anjum Jalal: Faisalabad Institute of Cardiology
Shahid Abbas: Faisalabad Institute of Cardiology
Philippe Frossard: Center for Non-Communicable Disease, Karachi
Christian Fuchsberger: University of Michigan
Lukas Forer: Medical University of Innsbruck
Sebastian Schoenherr: Medical University of Innsbruck
Qixin Bei: Genentech
Tushar Bhangale: Genentech
Jennifer Tom: Genentech
Santosh Gopi Krishna Gadde: Narayana Nethralaya Foundation
Priya B V: Narayana Nethralaya Foundation
Naveen Kumar Naik: Narayana Nethralaya Foundation
Minxian Wang: Broad Institute of MIT and Harvard
Pui-Yan Kwok: University of California
Amit V. Khera: Harvard Medical School
B. R. Lakshmi: MDCRC, Royal Care Super Speciality Hospital 1/520
Adam S. Butterworth: University of Cambridge
Rajiv Chowdhury: University of Cambridge
John Danesh: University of Cambridge
Emanuele Angelantonio: University of Cambridge
Aliya Naheed: Health Systems and Population Studies Division, icddr,b
Vinay Goyal: All India Institute of Medical Sciences (AIIMS)
Rukmini M. Kandadai: Nizams Institute of Medical Sciences (NIMS)
Hrishikesh Kumar: Institute of Neurosciences Kolkata
Rupam Borgohain: Nizams Institute of Medical Sciences (NIMS)
Adreesh Mukherjee: Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research (IPGME&R)
Pettarusp M. Wadia: Jaslok Hospital and Research Centre
Ravi Yadav: National Institute of Mental Health and Neurosciences (NIMHANS)
Soaham Desai: Bhaikaka University
Niraj Kumar: All India Institute of Medical Sciences
Atanu Biswas: Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research (IPGME&R)
Pramod Kumar Pal: National Institute of Mental Health and Neurosciences (NIMHANS)
Uday B. Muthane: Parkinson and Ageing Research Foundation
Shymal K. Das: Bangur Institute of Neurosciences and Institute of Post Graduate Medical Education and Research (IPGME&R)
Vedam L. Ramprasad: MedGenome Labs Pvt. Ltd.
Prashanth L. Kukkle: All India Institute of Medical Sciences
Somasekar Seshagiri: GenomeAsia 100K Foundation
Sekar Kathiresan: Broad Institute of MIT and Harvard
Arkasubhra Ghosh: Narayana Nethralaya Foundation
V. Mohan: Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre
Danish Saleheen: Center for Non-Communicable Disease, Karachi
Eric W. Stawiski: MedGenome Inc.
Andrew S. Peterson: MedGenome Inc.

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Date: 2023
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DOI: 10.1038/s41467-023-38766-1

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