Identification of sequence variants influencing immunoglobulin levels.
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Authors
Jonsson, StefanSveinbjornsson, Gardar
de Lapuente Portilla, Aitzkoa Lopez
Swaminathan, Bhairavi
Plomp, Rosina
Dekkers, Gillian
Ajore, Ram
Ali, Mina
Bentlage, Arthur E H
Elmér, Evelina
Eyjolfsson, Gudmundur I
Gudjonsson, Sigurjon A
Gullberg, Urban
Gylfason, Arnaldur
Halldorsson, Bjarni V
Hansson, Markus
Holm, Hilma
Johansson, Åsa
Johnsson, Ellinor
Jonasdottir, Aslaug
Ludviksson, Bjorn R
Oddsson, Asmundur
Olafsson, Isleifur
Olafsson, Sigurgeir
Sigurdardottir, Olof
Sigurdsson, Asgeir
Stefansdottir, Lilja
Masson, Gisli
Sulem, Patrick
Wuhrer, Manfred
Wihlborg, Anna-Karin
Thorleifsson, Gudmar
Gudbjartsson, Daniel F
Thorsteinsdottir, Unnur
Vidarsson, Gestur
Jonsdottir, Ingileif
Nilsson, Björn
Stefansson, Kari
Issue Date
2017-08
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Identification of sequence variants influencing immunoglobulin levels. 2017, 49 (8):1182-1191 Nat. Genet.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.Description
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https://www.nature.com/articles/ng.3897.pdfRights
Archived with thanks to Nature geneticsae974a485f413a2113503eed53cd6c53
10.1038/ng.3897
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