Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

South Asian Patient Population Genetics Reveal Strong Founder Effects and High Rates of Homozygosity – New Resources for Precision Medicine

Jeffrey D. Wall, J. Fah Sathirapongsasuti, Ravi Gupta, Anamitra Barik, Rajesh Kumar Rai, Asif Rasheed, Venkatesan Radha, Saurabh Belsare, Ramesh Menon, Sameer Phalke, Anuradha Mittal, John Fang, Deepak Tanneeru, Jacqueline Robinson, Ruchi Chaudhary, Christian Fuchsberger, Lukas Forer, Sebastian Schoenherr, Qixin Bei, Tushar Bhangale, Jennifer Tom, Santosh Gopi Krishna Gadde, B. V. Priya, Naveen Kumar Naik, Minxian Wang, Pui-Yan Kwok, Amit V. Khera, B. R. Lakshmi, Adam Butterworth, John Danesh, Sekar Seshagiri, Sekar Kathiresan, Arkasubhra Ghosh, V. Mohan, Abhijit Chowdhury, Danish Saleheen, Eric Stawiski, Andrew S. Peterson
doi: https://doi.org/10.1101/2020.10.02.323238
Jeffrey D. Wall
1Institute for Human Genetics, University of California, San Francisco, CA 94143, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jeff.wall@ucsf.edu peterson.andrew@genomeasia100k.org andrew.peterson@broadwing.bio
J. Fah Sathirapongsasuti
2MedGenome Inc. 348 Hatch Dr., Foster City, CA 94404 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ravi Gupta
3MedGenome Labs Pvt. Ltd., Bengaluru, Karnataka 560099, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anamitra Barik
4Society for Health and Demographic Surveillance, Suri 731101, West Bengal, India
5Chest Clinic, Niramoy TB Sanatorium, and District Hospital Birbhum, Department of Health and Family Welfare
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rajesh Kumar Rai
4Society for Health and Demographic Surveillance, Suri 731101, West Bengal, India
6Bernard Lown Scholar in Cardiovascular Health, Department of Global Health and Population, Harvard T H Chan School of Public Health, Boston, Massachusetts 02115, USA
7Department of Economics, and Centre for Modern Indian Studies, University of Göttingen, Göttingen 37073, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Asif Rasheed
8Center for Non-Communicable Disease, E50, 1, Block 9 Block 8 Gulshan-e-Iqbal, Karachi, Karachi City, Sindh 75300, Pakistan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Venkatesan Radha
9Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre, Chennai, Tamil Nadu 600086, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Saurabh Belsare
1Institute for Human Genetics, University of California, San Francisco, CA 94143, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ramesh Menon
3MedGenome Labs Pvt. Ltd., Bengaluru, Karnataka 560099, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sameer Phalke
3MedGenome Labs Pvt. Ltd., Bengaluru, Karnataka 560099, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anuradha Mittal
10Thermo Fisher Scientific, 3420 Central Expressway, Santa Clara, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John Fang
10Thermo Fisher Scientific, 3420 Central Expressway, Santa Clara, CA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Deepak Tanneeru
3MedGenome Labs Pvt. Ltd., Bengaluru, Karnataka 560099, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jacqueline Robinson
1Institute for Human Genetics, University of California, San Francisco, CA 94143, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ruchi Chaudhary
2MedGenome Inc. 348 Hatch Dr., Foster City, CA 94404 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christian Fuchsberger
11Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
12Institute for Biomedicine, Eurac Research, Bolzano, Italy
13Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lukas Forer
13Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sebastian Schoenherr
13Institute of Genetic Epidemiology, Department of Genetics and Pharmacology, Medical University of Innsbruck, Innsbruck, Austria
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qixin Bei
14Dept of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA, 94080, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tushar Bhangale
15Dept of Human Genetics, Genentech, 1 DNA Way, South San Francisco, CA 94080 USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer Tom
16Product Development Data Sciences, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Santosh Gopi Krishna Gadde
17Narayana Nethralaya Foundation, Bangalore, Karnataka 560010, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B. V. Priya
17Narayana Nethralaya Foundation, Bangalore, Karnataka 560010, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Naveen Kumar Naik
17Narayana Nethralaya Foundation, Bangalore, Karnataka 560010, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Minxian Wang
18Program in Medical and Population Genetics & Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pui-Yan Kwok
19Institute for Human Genetics, Cardiovascular Research Institute, and Department of Dermatology, UCSF
20Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amit V. Khera
18Program in Medical and Population Genetics & Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA
21Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
B. R. Lakshmi
22MDCRC, Royal Care Super Speciality Hospital 1/520, L & T Bye Pass Road, Neelambur, Coimbatore, Tamil Nadu - 641062
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adam Butterworth
23Cardiovascular Epidemiology Unit, Department of Public Health & Primary Care, University of Cambridge, Strangeways Research Laboratory, Wort’s Causeway, Cambridge, CB1 8RN, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John Danesh
23Cardiovascular Epidemiology Unit, Department of Public Health & Primary Care, University of Cambridge, Strangeways Research Laboratory, Wort’s Causeway, Cambridge, CB1 8RN, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sekar Seshagiri
24SciGenom Research Foundation, 55 First Floor, 1st Kamaraj Avenue, Kasturibai Nagar, Adyar, Chennai, Tamil Nadu 600020, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sekar Kathiresan
21Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
26Verve Therapeutics, 500 Technology Square, Suite 901, Cambridge, MA 02139
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Arkasubhra Ghosh
17Narayana Nethralaya Foundation, Bangalore, Karnataka 560010, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
V. Mohan
9Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialties Centre, Chennai, Tamil Nadu 600086, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Abhijit Chowdhury
4Society for Health and Demographic Surveillance, Suri 731101, West Bengal, India
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Danish Saleheen
8Center for Non-Communicable Disease, E50, 1, Block 9 Block 8 Gulshan-e-Iqbal, Karachi, Karachi City, Sindh 75300, Pakistan
25Seymour, Paul and Gloria Milstein Division of Cardiology at Columbia University, Irving Medical Center, 622 West 168th Street, Presbyterian Hospital Building PH-3, New York, NY 10032, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric Stawiski
2MedGenome Inc. 348 Hatch Dr., Foster City, CA 94404 USA
27PACT pharma, 2 Corporate Drive, South San Francisco, CA 94080
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew S. Peterson
2MedGenome Inc. 348 Hatch Dr., Foster City, CA 94404 USA
28Broadwing Bio, 171 Oyster Point Blvd, Suite 300, South San Francisco, CA 94080, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: jeff.wall@ucsf.edu peterson.andrew@genomeasia100k.org andrew.peterson@broadwing.bio
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Population-scale genetic studies can identify drug targets and allow disease risk to be predicted with resulting benefit for management of individual health risks and system-wide allocation of health care delivery resources. Although population-scale projects are underway in many parts of the world, genetic variation between population groups means that additional projects are warranted. South Asia has a population whose genetics is the least characterized of any of the world’s major populations. Here we describe GenomeAsia studies that characterize population structure in South Asia and that create tools for economical and accurate genotyping at population-scale. Prior work on population structure characterized isolated population groups, the relevance of which to large-scale studies of disease genetics is unclear. For our studies we used whole genome sequence information from 4,807 individuals recruited in the health care delivery systems of Pakistan, India and Bangladesh to ensure relevance to population-scale studies of disease genetics. We combined this with WGS data from 927 individuals from isolated South Asian population groups, and developed a custom SNP array (called SARGAM) that is optimized for future human genetic studies in South Asia. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of homozygosity that approach 100 times that seen in outbred populations. We describe founder effects that increase the power to associate functional variants with disease processes and that make South Asia a uniquely powerful place for population-scale genetic studies.

Competing Interest Statement

J. F. Sathirapongsasuti is an employee of MedGenome and a former employee of 23andMe. A. S. Peterson and E. Stawiski are former employees of MedGenome and Genentech. J. D. Wall is a consultant for MedGenome. R. Menon, S. Phalke, D. Tanneeru, R. Chaudhary and R. Gupta are employees of MedGenome. Q. Bei, T. Bhangale and J. Tom are employees of Genentech. A. Mittal and J. Fang are employees of Thermo Fisher Scientific.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted October 02, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
South Asian Patient Population Genetics Reveal Strong Founder Effects and High Rates of Homozygosity – New Resources for Precision Medicine
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
South Asian Patient Population Genetics Reveal Strong Founder Effects and High Rates of Homozygosity – New Resources for Precision Medicine
Jeffrey D. Wall, J. Fah Sathirapongsasuti, Ravi Gupta, Anamitra Barik, Rajesh Kumar Rai, Asif Rasheed, Venkatesan Radha, Saurabh Belsare, Ramesh Menon, Sameer Phalke, Anuradha Mittal, John Fang, Deepak Tanneeru, Jacqueline Robinson, Ruchi Chaudhary, Christian Fuchsberger, Lukas Forer, Sebastian Schoenherr, Qixin Bei, Tushar Bhangale, Jennifer Tom, Santosh Gopi Krishna Gadde, B. V. Priya, Naveen Kumar Naik, Minxian Wang, Pui-Yan Kwok, Amit V. Khera, B. R. Lakshmi, Adam Butterworth, John Danesh, Sekar Seshagiri, Sekar Kathiresan, Arkasubhra Ghosh, V. Mohan, Abhijit Chowdhury, Danish Saleheen, Eric Stawiski, Andrew S. Peterson
bioRxiv 2020.10.02.323238; doi: https://doi.org/10.1101/2020.10.02.323238
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
South Asian Patient Population Genetics Reveal Strong Founder Effects and High Rates of Homozygosity – New Resources for Precision Medicine
Jeffrey D. Wall, J. Fah Sathirapongsasuti, Ravi Gupta, Anamitra Barik, Rajesh Kumar Rai, Asif Rasheed, Venkatesan Radha, Saurabh Belsare, Ramesh Menon, Sameer Phalke, Anuradha Mittal, John Fang, Deepak Tanneeru, Jacqueline Robinson, Ruchi Chaudhary, Christian Fuchsberger, Lukas Forer, Sebastian Schoenherr, Qixin Bei, Tushar Bhangale, Jennifer Tom, Santosh Gopi Krishna Gadde, B. V. Priya, Naveen Kumar Naik, Minxian Wang, Pui-Yan Kwok, Amit V. Khera, B. R. Lakshmi, Adam Butterworth, John Danesh, Sekar Seshagiri, Sekar Kathiresan, Arkasubhra Ghosh, V. Mohan, Abhijit Chowdhury, Danish Saleheen, Eric Stawiski, Andrew S. Peterson
bioRxiv 2020.10.02.323238; doi: https://doi.org/10.1101/2020.10.02.323238

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4119)
  • Biochemistry (8828)
  • Bioengineering (6532)
  • Bioinformatics (23484)
  • Biophysics (11805)
  • Cancer Biology (9223)
  • Cell Biology (13336)
  • Clinical Trials (138)
  • Developmental Biology (7442)
  • Ecology (11425)
  • Epidemiology (2066)
  • Evolutionary Biology (15173)
  • Genetics (10453)
  • Genomics (14056)
  • Immunology (9187)
  • Microbiology (22199)
  • Molecular Biology (8823)
  • Neuroscience (47626)
  • Paleontology (351)
  • Pathology (1431)
  • Pharmacology and Toxicology (2493)
  • Physiology (3736)
  • Plant Biology (8090)
  • Scientific Communication and Education (1438)
  • Synthetic Biology (2224)
  • Systems Biology (6042)
  • Zoology (1254)