Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation (CROSBI ID 265105)
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Podaci o odgovornosti
Shen, Xia ; Klarić, Lucija ; Sharapov, Sodbo ; Mangino, Massimo ; Ning, Zheng ; Wu, Di ; Trbojević-Akmačić, Irena ; Pučić-Baković, Maja ; Rudan, Igor ; Polašek, Ozren ; Hayward, Caroline ; Spector, Timothy D. ; Wilson, James F. ; Lauc, Gordan ; Aulchenko, Yurii S.
engleski
Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation
Joint modeling of a number of phenotypes using multivariate methods has often been neglected in genome-wide association studies and if used, replication has not been sought. Modern omics technologies allow characterization of functional phenomena using a large number of related phenotype measures, which can benefit from such joint analysis. Here, we report a multivariate genome-wide association studies of 23 immunoglobulin G (IgG) N-glycosylation phenotypes. In the discovery cohort, our multi-phenotype method uncovers ten genome-wide significant loci, of which five are novel (IGH, ELL2, HLA-B-C, AZI1, FUT6-FUT3). We convincingly replicate all novel loci via multivariate tests. We show that IgG N-glycosylation loci are strongly enriched for genes expressed in the immune system, in particular antibody-producing cells and B lymphocytes. We empirically demonstrate the efficacy of multivariate methods to discover novel, reproducible pleiotropic effects.
GWAS
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Podaci o izdanju
Povezanost rada
Biologija, Interdisciplinarne prirodne znanosti, Kemija