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Nat Genet. 2017 Aug;49(8):1182-1191. doi: 10.1038/ng.3897. Epub 2017 Jun 19.

Identification of sequence variants influencing immunoglobulin levels.

Author information

1
deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.
2
Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund, Sweden.
3
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, the Netherlands.
4
Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
5
Clinical Immunology and Transfusion Medicine, Office of Medical Services, Lund, Sweden.
6
Laboratory in Mjodd, Reykjavik, Iceland.
7
School of Science and Engineering, Reykjavik University, Reykjavik, Iceland.
8
Department of Immunology, Landspitali, the National University Hospital of Iceland, Reykjavik, Iceland.
9
Department of Clinical Biochemistry, Landspitali, the National University Hospital of Iceland, Reykjavik, Iceland.
10
Department of Clinical Biochemistry, Akureyri Hospital, Akureyri, Iceland.
11
Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
12
School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
13
Broad Institute, Cambridge, Massachusetts, USA.

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.

PMID:
28628107
DOI:
10.1038/ng.3897
[Indexed for MEDLINE]

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