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Parental origin of sequence variants associated with complex diseases

Author

Listed:
  • Augustine Kong

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Valgerdur Steinthorsdottir

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Gisli Masson

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Gudmar Thorleifsson

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Patrick Sulem

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Soren Besenbacher

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Aslaug Jonasdottir

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Asgeir Sigurdsson

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Kari Th. Kristinsson

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Adalbjorg Jonasdottir

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Michael L. Frigge

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Arnaldur Gylfason

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Pall I. Olason

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Sigurjon A. Gudjonsson

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Sverrir Sverrisson

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Simon N. Stacey

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Bardur Sigurgeirsson

    (Department of Dermatology,)

  • Kristrun R. Benediktsdottir

    (Department of Pathology,)

  • Helgi Sigurdsson

    (Department of Oncology,)

  • Thorvaldur Jonsson

    (Department of Surgery,)

  • Rafn Benediktsson

    (Landspitali-University Hospital, 101 Reykjavik, Iceland)

  • Jon H. Olafsson

    (Department of Dermatology,)

  • Oskar Th. Johannsson

    (Department of Oncology,)

  • Astradur B. Hreidarsson

    (Landspitali-University Hospital, 101 Reykjavik, Iceland)

  • Gunnar Sigurdsson

    (Landspitali-University Hospital, 101 Reykjavik, Iceland)

  • Anne C. Ferguson-Smith

    (Development and Neuroscience, University of Cambridge)

  • Daniel F. Gudbjartsson

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland)

  • Unnur Thorsteinsdottir

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland
    Faculty of Medicine, University of Iceland)

  • Kari Stefansson

    (deCODE genetics, Sturlugata 8, 101 Reykjavík, Iceland
    Faculty of Medicine, University of Iceland)

Abstract

Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five—one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes—have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.

Suggested Citation

  • Augustine Kong & Valgerdur Steinthorsdottir & Gisli Masson & Gudmar Thorleifsson & Patrick Sulem & Soren Besenbacher & Aslaug Jonasdottir & Asgeir Sigurdsson & Kari Th. Kristinsson & Adalbjorg Jonasdo, 2009. "Parental origin of sequence variants associated with complex diseases," Nature, Nature, vol. 462(7275), pages 868-874, December.
    • Handle: RePEc:nat:nature:v:462:y:2009:i:7275:d:10.1038_nature08625
    DOI: 10.1038/nature08625
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    Cited by:

    1. Robin J. Hofmeister & Simone Rubinacci & Diogo M. Ribeiro & Alfonso Buil & Zoltán Kutalik & Olivier Delaneau, 2022. "Parent-of-Origin inference for biobanks," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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