Identification of sequence variants influencing immunoglobulin levels.

• Published in: Nature Genetics
• Main Authors: Jonsson, Stefan, Sveinbjornsson, 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
• Other Authors: 1 deCODE Genet Amgen Inc, Reykjavik, Iceland 2 Hematol & Transfus Med, Dept Lab Med, Lund, Sweden Show the Organization-Enhanced name(s) 3 Leiden Univ, Med Ctr, Ctr Prote & Metabol, Leiden, Netherlands Show the Organization-Enhanced name(s) 4 Univ Amsterdam, Expt Immunohematol Sanquin Res, Amsterdam, Netherlands Show the Organization-Enhanced name(s) 5 Univ Amsterdam, Acad Med Ctr, Landsteiner Lab, Amsterdam, Netherlands 6 Off Med Serv, Clin Immunol & Transfus Med, Lund, Sweden 7 Lab Mjodd, Reykjavik, Iceland Show the Organization-Enhanced name(s) 8 Reykjavik Univ, Sch Sci & Engn, Reykjavik, Iceland Show the Organization-Enhanced name(s) 9 Natl Univ Hosp Reykjavik, Landspitali, Dept Immunol, Reykjavik, Iceland Show the Organization-Enhanced name(s) 10 Natl Univ Hosp Reykjavik, Landspitali, Dept Clin Biochem, Reykjavik, Iceland 11 Akureyri Hosp, Dept Clin Biochem, Akureyri, Iceland Show the Organization-Enhanced name(s) 12 Univ Iceland, Sch Hlth Sci, Fac Med, Reykjavik, Iceland Show the Organization-Enhanced name(s) 13 Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland Show the Organization-Enhanced name(s) 14 Broad Inst, Cambridge, MA USA
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Publishing Group 2017
• Subjects: Ónæmiskerfi; Gen; AAI12; MAB12; NAF12; Cohort Studies; Female; Genetic Predisposition to Disease; Genetic Variation; Genome-Wide Association Study; Hematopoiesis; Humans; Iceland; Immunity; Humoral; Immunoglobulin Class Switching; Immunoglobulin Isotypes; Immunoglobulins; Male; Polymorphism; Single Nucleotide; Sweden
• Online Access: http://hdl.handle.net/2336/620331; https://doi.org/10.1038/ng.3897

To access publisher's full text version of this article click on the hyperlink below 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. Swedish Foundation for Strategic Research Marianne and Marcus Wallenberg Foundation Knut and Alice Wallenberg Foundation Swedish Research Council