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Identification of sequence variants influencing immunoglobulin levels

Jonsson, Stefan; Sveinbjornsson, Gardar; de Lapuente Portilla, Aitzkoa Lopez LU ; Swaminathan, Bhairavi LU ; Plomp, Rosina; Dekkers, Gillian; Ajore, Ram LU ; Ali, Mina LU ; Bentlage, Arthur E H and Elmér, Evelina LU , et al. (2017) In Nature Genetics 49(8). p.1182-1191
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... (More)

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.

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Nature Genetics
volume
49
issue
8
pages
1182 - 1191
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Nature Publishing Group
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  • scopus:85026400867
ISSN
1546-1718
DOI
10.1038/ng.3897
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English
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558c21dd-97ca-4bac-bbff-c4612faef84a
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2017-06-20 13:39:03
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2017-08-31 09:35:39
@article{558c21dd-97ca-4bac-bbff-c4612faef84a,
  abstract     = {<p>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&gt;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.</p>},
  author       = {Jonsson, Stefan and Sveinbjornsson, Gardar and de Lapuente Portilla, Aitzkoa Lopez and Swaminathan, Bhairavi and Plomp, Rosina and Dekkers, Gillian and Ajore, Ram and Ali, Mina and Bentlage, Arthur E H and Elmér, Evelina and Eyjolfsson, Gudmundur Ingi and Gudjonsson, Sigurjon A. and Gullberg, Urban and Gylfason, Arnaldur and Halldorsson, Bjarni V. and Hansson, Markus and Holm, Hilma and Johansson, Åsa and Johnsson, Ellinor and Jonasdottir, Aslaug and Ludviksson, Bjorn R and Oddsson, Asmundur and Olafsson, Isleifur and Olafsson, Sigurgeir and Sigurdardottir, Olof and Sigurdsson, Asgeir and Stefansdottir, Lilja and Masson, Gisli and Sulem, Patrick and Wuhrer, Manfred and Wihlborg, Anna-Karin and Thorleifsson, Gudmar and Gudbjartsson, Daniel F. and Thorsteinsdottir, Unnur and Vidarsson, Gestur and Jonsdottir, Ingileif and Nilsson, Björn and Stefansson, Kari},
  issn         = {1546-1718},
  language     = {eng},
  month        = {06},
  number       = {8},
  pages        = {1182--1191},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Identification of sequence variants influencing immunoglobulin levels},
  url          = {http://dx.doi.org/10.1038/ng.3897},
  volume       = {49},
  year         = {2017},
}