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

41 Pages Posted: 9 Nov 2020 Publication Status: Review Complete

See all articles by Jeff D. Wall

Jeff D. Wall

University of California, San Francisco (UCSF) - Institute for Human Genetics

J. Fah Sathirapongsasuti

MedGenome Inc.

Ravi Gupta

MedGenome Labs Pvt. Ltd.

Anamitra Barik

Society for Health and Demographic Surveillance

Rajesh Kumar Rai

Society for Health and Demographic Surveillance

Asif Rasheed

Center for Non-Communicable Diseases

Venkatesan Radha

Madras Diabetes Research Foundation

Saurabh Belsare

University of California, San Francisco (UCSF) - Institute for Human Genetics

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, San Francisco (UCSF) - Institute for Human Genetics

Ruchi Chaudhary

MedGenome Inc.

Zameer-ul Asar

Center for Non-Communicable Diseases

Imran Saleem

Center for Non-Communicable Diseases

Unzila Ishtiaq

Center for Non-Communicable Diseases

Areej Fatima

Center for Non-Communicable Diseases

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 Diseases

Christian Fuchsberger

University of Michigan at Ann Arbor - Department of Biostatistics

Lukas Forer

Medical University of Innsbruck - Institute of Genetic Epidemiology

Sebastian Schoenherr

Medical University of Innsbruck - Institute of Genetic Epidemiology

Qixin Bei

Genentech, Inc. - San Francisco - Department of Molecular Biology

Tushar Bhangale

Genentech, Inc. - San Francisco - Department of Human Genetics

Jennifer Tom

Genentech, Inc. - San Francisco - Product Development Data Sciences

Santosh Gopi Krishna Gadde

Narayana Nethralaya Foundation

Priya B. V.

Narayana Nethralaya Foundation

Naveen Kumar Naik

Narayana Nethralaya Foundation

Minxian Wang

Massachusetts Institute of Technology and Harvard University - Program in Medical and Population Genetics

Pui-Yan Kwok

University of California, San Francisco (UCSF) - Institute for Human Genetics

Amit V. Khera

Massachusetts Institute of Technology and Harvard University - Program in Medical and Population Genetics

B. R. Lakshmi

Royal Care Super Speciality Hospital - MDCRC

Adam S. Butterworth

University of Cambridge - British Heart Foundation Cardiovascular Epidemiology Unit

Rajiv Chowdhury

University of Cambridge - British Heart Foundation Cardiovascular Epidemiology Unit

John Danesh

University of Cambridge - Department of Public Health and Primary Care

Emanuele di Angelantonio

University of Cambridge - British Heart Foundation Cardiovascular Epidemiology Unit

Aliya Naheed

International Centre for Diarrhoeal Disease Research - Initiative for Non Communicable Diseases

Sekar Seshagiri

Massachusetts Institute of Technology and Harvard University - Program in Medical and Population Genetics

Sekar Kathiresan

Harvard University - Center for Genomic Medicine

Arkasubhra Ghosh

Narayana Nethralaya Foundation

V. Mohan

Madras Diabetes Research Foundation

Abhijit Chowdhury

Society for Health and Demographic Surveillance

Danish Saleheen

Center for Non-Communicable Diseases

Eric Stawiski

MedGenome Inc.

Andrew S. Peterson

Genentech, Inc. - San Francisco

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Abstract

Here we characterize population structure in South Asia and create a genotyping array and imputation reference panel that are optimized for South Asian Genomes and that allow accurate and economical 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. 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 find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of homozygosity that reach 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.

Keywords: human genetics, Medical Genetics, Precision Medicine, Diverse Populations, South Asia, Homozygosity, Consaingunity, Endogamy, Recessive

Suggested Citation

Wall, Jeff D. and Sathirapongsasuti, J. Fah and Gupta, Ravi and Barik, Anamitra and Rai, Rajesh Kumar and Rasheed, Asif and Radha, Venkatesan and Belsare, Saurabh and Menon, Ramesh and Phalke, Sameer and Mittal, Anuradha and Fang, John and Tanneeru, Deepak and Deshmukh, Manjari and Bassi, Akshi and Robinson, Jacqueline and Chaudhary, Ruchi and Asar, Zameer-ul and Saleem, Imran and Ishtiaq, Unzila and Fatima, Areej and Sheikh, Saqib Shafi and Hameed, Shahid and Ishaq, Mohammad and Rasheed, Syed Zahed and Memon, Fazal-ur-Rehman and Jalal, Anjum and Abbas, Shahid and Frossard, Philippe and Fuchsberger, Christian and Forer, Lukas and Schoenherr, Sebastian and Bei, Qixin and Bhangale, Tushar and Tom, Jennifer and Gadde, Santosh Gopi Krishna and V., Priya B. and Naik, Naveen Kumar and Wang, Minxian and Kwok, Pui-Yan and Khera, Amit V. and Lakshmi, B. R. and Butterworth, Adam S. and Chowdhury, Rajiv and Danesh, John and di Angelantonio, Emanuele and Naheed, Aliya and Seshagiri, Sekar and Kathiresan, Sekar and Ghosh, Arkasubhra and Mohan, V. and Chowdhury, Abhijit and Saleheen, Danish and Stawiski, Eric and Peterson, Andrew S., South Asian Patient Population Genetics Reveal Strong Founder Effects and High Rates of Homozygosity – New Resources for Precision Medicine. Available at SSRN: https://ssrn.com/abstract=3728138 or http://dx.doi.org/10.2139/ssrn.3728138
This version of the paper has not been formally peer reviewed.

Jeff D. Wall

University of California, San Francisco (UCSF) - Institute for Human Genetics ( email )

Third Avenue and Parnassus
San Francisco, CA 94143
United States

J. Fah Sathirapongsasuti

MedGenome Inc. ( email )

United States

Ravi Gupta

MedGenome Labs Pvt. Ltd.

Anamitra Barik

Society for Health and Demographic Surveillance

Rajesh Kumar Rai

Society for Health and Demographic Surveillance

Asif Rasheed

Center for Non-Communicable Diseases

Karachi
Pakistan

Venkatesan Radha

Madras Diabetes Research Foundation

Chennai
India

Saurabh Belsare

University of California, San Francisco (UCSF) - Institute for Human Genetics

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Ramesh Menon

MedGenome Labs Pvt. Ltd.

Sameer Phalke

MedGenome Labs Pvt. Ltd.

Anuradha Mittal

Thermo Fisher Scientific

Cambridge, OR
United Kingdom

John Fang

Thermo Fisher Scientific

Cambridge, OR
United Kingdom

Deepak Tanneeru

MedGenome Labs Pvt. Ltd.

Manjari Deshmukh

MedGenome Labs Pvt. Ltd.

Akshi Bassi

MedGenome Labs Pvt. Ltd.

Jacqueline Robinson

University of California, San Francisco (UCSF) - Institute for Human Genetics

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Ruchi Chaudhary

MedGenome Inc.

United States

Zameer-ul Asar

Center for Non-Communicable Diseases

Karachi
Pakistan

Imran Saleem

Center for Non-Communicable Diseases

Karachi
Pakistan

Unzila Ishtiaq

Center for Non-Communicable Diseases

Karachi
Pakistan

Areej Fatima

Center for Non-Communicable Diseases

Karachi
Pakistan

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 Diseases

Karachi
Pakistan

Christian Fuchsberger

University of Michigan at Ann Arbor - Department of Biostatistics

500 S. State Street
Ann Arbor, MI 48109
United States

Lukas Forer

Medical University of Innsbruck - Institute of Genetic Epidemiology

Innrain 52
Christoph-Probst-Platz
Innsbruck, 6020
Austria

Sebastian Schoenherr

Medical University of Innsbruck - Institute of Genetic Epidemiology

Innrain 52
Christoph-Probst-Platz
Innsbruck, 6020
Austria

Qixin Bei

Genentech, Inc. - San Francisco - Department of Molecular Biology

1 DNA Way
South San Francisco, CA 94080-4990
United States

Tushar Bhangale

Genentech, Inc. - San Francisco - Department of Human Genetics

1 DNA Way
South San Francisco, CA 94080-4990
United States

Jennifer Tom

Genentech, Inc. - San Francisco - Product Development Data Sciences

1 DNA Way
South San Francisco, CA 94080-4990
United States

Santosh Gopi Krishna Gadde

Narayana Nethralaya Foundation

Priya B. V.

Narayana Nethralaya Foundation

Naveen Kumar Naik

Narayana Nethralaya Foundation

Minxian Wang

Massachusetts Institute of Technology and Harvard University - Program in Medical and Population Genetics

Massachusetts, MA
United States

Pui-Yan Kwok

University of California, San Francisco (UCSF) - Institute for Human Genetics

Third Avenue and Parnassus
San Francisco, CA 94143
United States

Amit V. Khera

Massachusetts Institute of Technology and Harvard University - Program in Medical and Population Genetics

Massachusetts, MA
United States

B. R. Lakshmi

Royal Care Super Speciality Hospital - MDCRC

Adam S. Butterworth

University of Cambridge - British Heart Foundation Cardiovascular Epidemiology Unit

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Rajiv Chowdhury

University of Cambridge - British Heart Foundation Cardiovascular Epidemiology Unit

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

John Danesh

University of Cambridge - Department of Public Health and Primary Care

Cambridge
United Kingdom

Emanuele Di Angelantonio

University of Cambridge - British Heart Foundation Cardiovascular Epidemiology Unit

Trinity Ln
Cambridge, CB2 1TN
United Kingdom

Aliya Naheed

International Centre for Diarrhoeal Disease Research - Initiative for Non Communicable Diseases

68 Shaheed Tajuddin Ahmed Sarani
Dhaka, 1212
Bangladesh

Sekar Seshagiri

Massachusetts Institute of Technology and Harvard University - Program in Medical and Population Genetics

Massachusetts, MA
United States

Sekar Kathiresan

Harvard University - Center for Genomic Medicine ( email )

185 Cambridge Street
Boston, MA 02114
United States

Arkasubhra Ghosh

Narayana Nethralaya Foundation

V. Mohan

Madras Diabetes Research Foundation

Chennai
India

Abhijit Chowdhury

Society for Health and Demographic Surveillance

Danish Saleheen

Center for Non-Communicable Diseases

Karachi
Pakistan

Eric Stawiski

MedGenome Inc. ( email )

United States

Andrew S. Peterson (Contact Author)

Genentech, Inc. - San Francisco

1 DNA Way
South San Francisco, CA 94080-4990
United States

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