biostudies-literatureLauc GMedical Research CouncilChief Scientist OfficeWellcome Truste1003225https://www.ebi.ac.uk/biostudies/studies/S-EPMC3561084biostudies-literatureUnknown9(1)Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. Four loci coPLoS geneticsLoci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.PMC3561084CZB/4/710CZB/4/728MC_PC_U127561128095831Zgaga LUh HWDeelder AMAdamczyk BPolasek OHuffman JEKolcic ISlagboom PEKeser TBeekman MRuhaak LRSwann OWilson JFWuhrer MRudd PMScheijen Bvan Leeuwen FNde Craen AJPucic MLukic IKGornik OWang WHouwing-Duistermaat JJHayward CZeng QRudan IMcKeigue PHastie NDWright AFPatrick ALNovokmet MVitart VMolokhia MMuzinic AGyllensten UCampbell HAulchenko YKristic JLauc GfalseLoci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.Glycosylation of immunoglobulin G (IgG) influences IgG effector function by modulating binding to Fc receptors. To identify genetic loci associated with IgG glycosylation, we quantitated N-linked IgG glycans using two approaches. After isolating IgG from human plasma, we performed 77 quantitative measurements of N-glycosylation using ultra-performance liquid chromatography (UPLC) in 2,247 individuals from four European discovery populations. In parallel, we measured IgG N-glycans using MALDI-TOF mass spectrometry (MS) in a replication cohort of 1,848 Europeans. Meta-analysis of genome-wide association study (GWAS) results identified 9 genome-wide significant loci (P<2.27 × 10(-9)) in the discovery analysis and two of the same loci (B4GALT1 and MGAT3) in the replication cohort. Four loci co2013-01-01T00:00:00Z20132026-04-08T04:19:05.006Z2026-04-07T21:53:07.516ZS-EPMC35610842338269110.1371/journal.pgen.1003225