Nature Communications (Jun 2023)
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 di 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,
- Andrew S. Peterson
Affiliations
- Jeffrey D. Wall
- Institute for Human Genetics, 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
- Institute for Human Genetics, 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
- Institute for Human Genetics, 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
- Department of Biostatistics, University of Michigan
- Lukas Forer
- Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck
- Sebastian Schoenherr
- Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck
- Qixin Bei
- Department of Molecular Biology, Genentech
- Tushar Bhangale
- Department of Human Genetics, Genentech
- Jennifer Tom
- Product Development Data Sciences, Genentech
- Santosh Gopi Krishna Gadde
- Narayana Nethralaya Foundation
- Priya B V
- Narayana Nethralaya Foundation
- Naveen Kumar Naik
- Narayana Nethralaya Foundation
- Minxian Wang
- Program in Medical and Population Genetics & Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard
- Pui-Yan Kwok
- Institute for Human Genetics, University of California
- Amit V. Khera
- Harvard Medical School
- B. R. Lakshmi
- MDCRC, Royal Care Super Speciality Hospital 1/520
- Adam S. Butterworth
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
- Rajiv Chowdhury
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
- John Danesh
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
- Emanuele di Angelantonio
- British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge
- Aliya Naheed
- Initiative for Non Communicable Diseases, 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
- Shree Krishna Hospital and Pramukhaswami Medical College, 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
- Program in Medical and Population Genetics & Cardiovascular Disease Initiative, 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.
- DOI
- https://doi.org/10.1038/s41467-023-38766-1
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 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.
