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Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania

Author

Listed:
  • Tom Parks

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Mariana M. Mirabel

    (Paris Centre de Recherche Cardiovasculaire, Institut National de la Santé et de la Recherche Médicale, Hôpital Européen Georges Pompidou)

  • Joseph Kado

    (Ministry of Health and Medical Services, Colonial War Memorial Hospital
    College of Medicine, Nursing & Health Sciences, Fiji National University)

  • Kathryn Auckland

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Jaroslaw Nowak

    (University of Oxford)

  • Anna Rautanen

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Alexander J. Mentzer

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Eloi Marijon

    (Paris Centre de Recherche Cardiovasculaire, Institut National de la Santé et de la Recherche Médicale, Hôpital Européen Georges Pompidou
    Faculté de Médecine Paris Descartes, Université Paris Descartes)

  • Xavier Jouven

    (Paris Centre de Recherche Cardiovasculaire, Institut National de la Santé et de la Recherche Médicale, Hôpital Européen Georges Pompidou
    Faculté de Médecine Paris Descartes, Université Paris Descartes)

  • Mai Ling Perman

    (College of Medicine, Nursing & Health Sciences, Fiji National University)

  • Tuliana Cua

    (Rheumatic Heart Disease Control Programme, Ministry of Health and Medical Services, Colonial War Memorial Hospital)

  • John K. Kauwe

    (College of Life Sciences, Brigham Young University)

  • John B. Allen

    (College of Life Sciences, Brigham Young University)

  • Henry Taylor

    (Rheumatic Heart Disease Control Programme, Samoa Ministry of Health)

  • Kathryn J. Robson

    (MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington)

  • Charlotte M. Deane

    (University of Oxford)

  • Andrew C. Steer

    (Centre for International Child Health, University of Melbourne
    Murdoch Children’s Research Institute)

  • Adrian V. S. Hill

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

Abstract

The indigenous populations of the South Pacific experience a high burden of rheumatic heart disease (RHD). Here we report a genome-wide association study (GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian countries. Stratifying by ancestry, we analysed genotyped and imputed variants in Melanesians (607 cases and 1,229 controls) before follow-up of suggestive loci in three further ancestral groups: Polynesians, South Asians and Mixed or other populations (totalling 399 cases and 617 controls). We identify a novel susceptibility signal in the immunoglobulin heavy chain (IGH) locus centring on a haplotype of nonsynonymous variants in the IGHV4-61 gene segment corresponding to the IGHV4-61*02 allele. We show each copy of IGHV4-61*02 is associated with a 1.4-fold increase in the risk of RHD (odds ratio 1.43, 95% confidence intervals 1.27–1.61, P=4.1 × 10−9). These findings provide new insight into the role of germline variation in the IGH locus in disease susceptibility.

Suggested Citation

  • Tom Parks & Mariana M. Mirabel & Joseph Kado & Kathryn Auckland & Jaroslaw Nowak & Anna Rautanen & Alexander J. Mentzer & Eloi Marijon & Xavier Jouven & Mai Ling Perman & Tuliana Cua & John K. Kauwe &, 2017. "Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania," Nature Communications, Nature, vol. 8(1), pages 1-10, August.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14946
    DOI: 10.1038/ncomms14946
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    Cited by:

    1. Oscar L. Rodriguez & Yana Safonova & Catherine A. Silver & Kaitlyn Shields & William S. Gibson & Justin T. Kos & David Tieri & Hanzhong Ke & Katherine J. L. Jackson & Scott D. Boyd & Melissa L. Smith , 2023. "Genetic variation in the immunoglobulin heavy chain locus shapes the human antibody repertoire," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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