Identification of sequence variants influencing immunoglobulin levels

Research output: Contribution to journalArticle

Abstract

Immunoglobulins are the effector molecules of the adaptive humoral immune system. In a genome-wide association study of 19,219 individuals, we found 38 new variants and replicated 5 known variants associating with IgA, IgG or IgM levels or with composite immunoglobulin traits, accounted for by 32 loci. Variants at these loci also affect the risk of autoimmune diseases and blood malignancies and influence blood cell development. Notable associations include a rare variant at RUNX3 decreasing IgA levels by shifting isoform proportions (rs188468174[C>T]: P = 8.3 × 10(-55), β = -0.90 s.d.), a rare in-frame deletion in FCGR2B abolishing IgG binding to the encoded receptor (p.Asn106del: P = 4.2 × 10(-8), β = 1.03 s.d.), four IGH locus variants influencing class switching, and ten new associations with the HLA region. Our results provide new insight into the regulation of humoral immunity.

Details

Authors
  • Stefan Jonsson
  • Gardar Sveinbjornsson
  • Bhairavi Swaminathan
  • Rosina Plomp
  • Gillian Dekkers
  • Mina Ali
  • Arthur E H Bentlage
  • Gudmundur Ingi Eyjolfsson
  • Sigurjon A. Gudjonsson
  • Arnaldur Gylfason
  • Bjarni V. Halldorsson
  • Hilma Holm
  • Åsa Johansson
  • Ellinor Johnsson
  • Aslaug Jonasdottir
  • Bjorn R Ludviksson
  • Asmundur Oddsson
  • Isleifur Olafsson
  • Sigurgeir Olafsson
  • Olof Sigurdardottir
  • Asgeir Sigurdsson
  • Lilja Stefansdottir
  • Gisli Masson
  • Patrick Sulem
  • Manfred Wuhrer
  • Gudmar Thorleifsson
  • Daniel F. Gudbjartsson
  • Unnur Thorsteinsdottir
  • Gestur Vidarsson
  • Ingileif Jonsdottir
  • Kari Stefansson
Organisations
External organisations
  • deCODE Genetics/Amgen, Inc.
  • Laboratory in Mjodd, Reykjavik
  • Reykjavik University
  • National University Hospital of Iceland
  • University of Iceland
  • Leiden University Medical Centre
  • University of Amsterdam
  • Broad Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
Original languageEnglish
Pages (from-to)1182-1191
JournalNature Genetics
Volume49
Issue number8
Early online date2017 Jun 19
Publication statusPublished - 2017
Publication categoryResearch
Peer-reviewedYes

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