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

Author

Listed:
  • Jeffrey D. Wall

    (University of California
    California Academy of Sciences)

  • J. Fah Sathirapongsasuti

    (MedGenome Inc.
    GenomeAsia 100K Foundation)

  • 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
    Institute for Biomedicine, Eurac Research
    Medical University of Innsbruck)

  • 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
    University of California San Francisco
    Academia Sinica)

  • Amit V. Khera

    (Harvard Medical School
    Brigham and Women’s Hospital
    Verve Therapeutics)

  • B. R. Lakshmi

    (MDCRC, Royal Care Super Speciality Hospital 1/520)

  • Adam S. Butterworth

    (University of Cambridge
    University of Cambridge
    University of Cambridge and Cambridge University Hospitals
    Wellcome Genome Campus and University of Cambridge)

  • Rajiv Chowdhury

    (University of Cambridge)

  • John Danesh

    (University of Cambridge
    University of Cambridge
    University of Cambridge and Cambridge University Hospitals
    Wellcome Genome Campus and University of Cambridge)

  • Emanuele Angelantonio

    (University of Cambridge
    University of Cambridge
    University of Cambridge and Cambridge University Hospitals
    Wellcome Genome Campus and University of Cambridge)

  • Aliya Naheed

    (Health Systems and Population Studies Division, icddr,b)

  • Vinay Goyal

    (All India Institute of Medical Sciences (AIIMS)
    Medanta Hospital
    Medanta, The Medicity)

  • 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
    Manipal Hospital
    Parkinson’s Disease and Movement Disorders Clinic)

  • Somasekar Seshagiri

    (GenomeAsia 100K Foundation
    Genentech)

  • Sekar Kathiresan

    (Broad Institute of MIT and Harvard
    Verve Therapeutics
    Massachusetts General Hospital)

  • 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
    Seymour, Paul and Gloria Milstein Division of Cardiology at Columbia University)

  • Eric W. Stawiski

    (MedGenome Inc.
    GenomeAsia 100K Foundation
    Genentech
    Caribou Biosciences)

  • Andrew S. Peterson

    (MedGenome Inc.
    GenomeAsia 100K Foundation
    Genentech
    Broadwing Bio)

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.

Suggested Citation

  • 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 Des, 2023. "South Asian medical cohorts reveal strong founder effects and high rates of homozygosity," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38766-1
    DOI: 10.1038/s41467-023-38766-1
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    as
    1. Swapan Mallick & Heng Li & Mark Lipson & Iain Mathieson & Melissa Gymrek & Fernando Racimo & Mengyao Zhao & Niru Chennagiri & Susanne Nordenfelt & Arti Tandon & Pontus Skoglund & Iosif Lazaridis & Sri, 2016. "The Simons Genome Diversity Project: 300 genomes from 142 diverse populations," Nature, Nature, vol. 538(7624), pages 201-206, October.
    2. Monkol Lek & Konrad J. Karczewski & Eric V. Minikel & Kaitlin E. Samocha & Eric Banks & Timothy Fennell & Anne H. O’Donnell-Luria & James S. Ware & Andrew J. Hill & Beryl B. Cummings & Taru Tukiainen , 2016. "Analysis of protein-coding genetic variation in 60,706 humans," Nature, Nature, vol. 536(7616), pages 285-291, August.
    3. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    4. Alex Diaz-Papkovich & Luke Anderson-Trocmé & Chief Ben-Eghan & Simon Gravel, 2019. "UMAP reveals cryptic population structure and phenotype heterogeneity in large genomic cohorts," PLOS Genetics, Public Library of Science, vol. 15(11), pages 1-24, November.
    5. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
    6. David Reich & Kumarasamy Thangaraj & Nick Patterson & Alkes L. Price & Lalji Singh, 2009. "Reconstructing Indian population history," Nature, Nature, vol. 461(7263), pages 489-494, September.
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