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Sharapov, S.Z.* ; Tsepilov, Y.A.* ; Klaric, L.* ; Mangino, M.* ; Thareja, G.* ; Shadrina, A.S.* ; Simurina, M.* ; Dagostino, C.* ; Dmitrieva, J.* ; Vilaj, M.* ; Vučković, F.* ; Pavić, T.* ; Stambuk, J.* ; Trbojević-Akmačić, I.* ; Krištić, J.* ; Simunovic, J.* ; Momcilovic, A.* ; Campbell, H.* ; Doherty, M.* ; Dunlop, M.G.* ; Farrington, S.M.* ; Pučić-Baković, M.* ; Gieger, C. ; Allegri, M.* ; Louis, E.* ; Georges, M.* ; Suhre, K.* ; Spector, T.* ; Williams, F.M.K.* ; Lauc, G.* ; Aulchenko, Y.S.*

Defining the genetic control of human blood plasma N-glycome using genome-wide association study.

Hum. Mol. Genet. 28, 2062-2077 (2019)
Verlagsversion Postprint Forschungsdaten DOI
Open Access Green
Glycosylation is a common post-translational modification of proteins. Glycosylation is associated with a number of human diseases. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people measured by Ultra Performance Liquid Chromatography (UPLC) technology. Starting with the 36 original traits measured by UPLC, we computed an additional 77 derived traits leading to a total of 113 glycan traits. We studied associations between these traits and genetic polymorphisms located on human autosomes. We discovered and replicated 12 loci. This allowed us to demonstrate an overlap in genetic control between total plasma protein and IgG glycosylation. The majority of revealed loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3 and MGAT5) and a known regulator of plasma protein fucosylation (HNF1A). However, we also found loci that could possibly reflect other more complex aspects of glycosylation process. Functional genomic annotation suggested the role of several genes including DERL3, CHCHD10, TMEM121, IGH and IKZF1. The hypotheses we generated may serve as a starting point for further functional studies in this research area.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Immunoglobulin-g; Glycosylation; Protein; Loci; Glycans; Disease; Identification; Expression; Mechanisms; Mutations
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Quellenangaben Band: 28, Heft: 12, Seiten: 2062-2077 Artikelnummer: , Supplement: ,
Verlag Oxford University Press
Verlagsort Great Clarendon St, Oxford Ox2 6dp, England
Begutachtungsstatus Peer reviewed