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

JD Wall; JF Sathirapongsasuti; R Gupta; A Rasheed; R Venkatesan; S Belsare; R Menon; S Phalke; A Mittal; J Fang; D Tanneeru; M Deshmukh; A Bassi; J Robinson; R Chaudhary; S Murugan; Z Ul-Asar; I Saleem; U Ishtiaq; A Fatima; SS Sheikh; S Hameed; M Ishaq; SZ Rasheed; FU Memon; A Jalal; S Abbas; P Frossard; Christian Fuchsberger; L Forer; S Schoenherr; Q Bei; T Bhangale; J Tom; SGK Gadde; P B V; NK Naik; M Wang; PY Kwok; AV Khera; BR Lakshmi; AS Butterworth; R Chowdhury; J Danesh; E di Angelantonio; A Naheed; V Goyal; RM Kandadai; H Kumar; R Borgohain; A Mukherjee; PM Wadia; R Yadav; S Desai; N Kumar; A Biswas; PK Pal; UB Muthane; SK Das; VL Ramprasad; PL Kukkle; S Seshagiri; S Kathiresan; A Ghosh; V Mohan; D Saleheen; EW Stawiski; AS Peterson

doi:10.1038/s41467-023-38766-1

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

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

JD Wall, JF Sathirapongsasuti, R Gupta, A Rasheed, R Venkatesan, S Belsare, R Menon, S Phalke, A Mittal, J Fang, …

Nature Communications, Vol.14(1)

08/06/2023

DOI: https://doi.org/10.1038/s41467-023-38766-1

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https://hdl.handle.net/10863/36551

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.

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Title: South Asian medical cohorts reveal strong founder effects and high rates of homozygosity
Creators: JD Wall - University of California, San Francisco
JF Sathirapongsasuti
R Gupta - SciGenom Labs
A Rasheed - Center for Non-Communicable Diseases
R Venkatesan
S Belsare - University of California, San Francisco
R Menon - SciGenom Labs
S Phalke - SciGenom Labs
A Mittal - Thermo Fisher Scientific
J Fang - Thermo Fisher Scientific
D Tanneeru - SciGenom Labs
M Deshmukh - SciGenom Labs
A Bassi - SciGenom Labs
J Robinson - University of California, San Francisco
R Chaudhary
S Murugan - SciGenom Labs
Z Ul-Asar - Center for Non-Communicable Diseases
I Saleem - Center for Non-Communicable Diseases
U Ishtiaq - Center for Non-Communicable Diseases
A Fatima - Center for Non-Communicable Diseases
SS Sheikh - Punjab Institute of Cardiology
S Hameed - Punjab Institute of Cardiology
M Ishaq - Karachi Institute of Heart Diseases
SZ Rasheed - Karachi Institute of Heart Diseases
FU Memon
A Jalal - University of Faisalabad
S Abbas - University of Faisalabad
P Frossard - Center for Non-Communicable Diseases
Christian Fuchsberger - University of Michigan–Ann Arbor
L Forer - Innsbruck Medical University
S Schoenherr - Innsbruck Medical University
Q Bei
T Bhangale
J Tom
SGK Gadde
P B V
NK Naik - Narayana Nethralaya
M Wang - Broad Institute
PY Kwok - University of California, San Francisco
AV Khera - Harvard University
BR Lakshmi
AS Butterworth - Health Data Research UK
R Chowdhury - British Heart Foundation
J Danesh - Wellcome Sanger Institute
E di Angelantonio - Genomics
A Naheed - International Centre for Diarrhoeal Disease Research
V Goyal - Medanta The Medicity
RM Kandadai - Nizam's Institute of Medical Sciences
H Kumar - Institute of Neurosciences Kolkata
R Borgohain - Nizam's Institute of Medical Sciences
A Mukherjee - Bangur Institute of Neurosciences
PM Wadia - Jaslok Hospital
R Yadav - National Institute of Mental Health and Neurosciences
S Desai - Pramukhswami Medical College
N Kumar - All India Institute of Medical Sciences
A Biswas - Institute of Post Graduate Medical Education and Research
PK Pal - National Institute of Mental Health and Neurosciences
UB Muthane - Parkinson’s Disease Foundation of India
SK Das - Bangur Institute of Neurosciences
VL Ramprasad
PL Kukkle - All India Institute of Medical Sciences
S Seshagiri
S Kathiresan - Broad Institute
A Ghosh - Narayana Nethralaya
V Mohan - Madras Diabetes Research Foundation
D Saleheen - Center for Non-Communicable Diseases
EW Stawiski - Caribou Biosciences
AS Peterson
Publication Details: Nature Communications, Vol.14(1)
EISSN: 2041-1723
Series / Volume: 14
Publisher: Springer Science and Business Media LLC
Identifiers: (EURAC)27624674
991006612097401241
Web of Science ID: P0GO8
Copyright: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Academic Unit: Institute for Biomedicine
Language: English
Resource Type: Journal article
Description coverage: international
Description audience: Scientific
Local Fields: Scientific
Author Names String: Wall JD, Sathirapongsasuti JF, Gupta R, Rasheed A, Venkatesan R, Belsare S, Menon R, Phalke S, Mittal A, Fang J, Tanneeru D, Deshmukh M, Bassi A, Robinson J, Chaudhary R, Murugan S, Ul-Asar Z, Saleem I, Ishtiaq U, Fatima A, Sheikh SS, Hameed S, Ishaq M, Rasheed SZ, Memon FU, Jalal A, Abbas S, Frossard P, Fuchsberger C, Forer L, Schoenherr S, Bei Q, Bhangale T, Tom J, Gadde SGK, B V P, Naik NK, Wang M, Kwok PY, Khera AV, Lakshmi BR, Butterworth AS, Chowdhury R, Danesh J, di Angelantonio E, Naheed A, Goyal V, Kandadai RM, Kumar H, Borgohain R, Mukherjee A, Wadia PM, Yadav R, Desai S, Kumar N, Biswas A, Pal PK, Muthane UB, Das SK, Ramprasad VL, Kukkle PL, Seshagiri S, Kathiresan S, Ghosh A, Mohan V, Saleheen D, Stawiski EW, Peterson AS

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