Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation

Xia Shen (), Lucija Klarić, Sodbo Sharapov, Massimo Mangino, Zheng Ning, Di Wu, Irena Trbojević-Akmačić, Maja Pučić-Baković, Igor Rudan, Ozren Polašek, Caroline Hayward, Timothy D. Spector, James F. Wilson, Gordan Lauc and Yurii S. Aulchenko ()
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Xia Shen: University of Edinburgh
Lucija Klarić: University of Edinburgh
Sodbo Sharapov: Novosibirsk State University
Massimo Mangino: King’s College London
Zheng Ning: Karolinska Institutet
Di Wu: Stockholm University
Irena Trbojević-Akmačić: Genos Glycoscience Research Laboratory
Maja Pučić-Baković: Genos Glycoscience Research Laboratory
Igor Rudan: University of Edinburgh
Ozren Polašek: University of Split
Caroline Hayward: University of Edinburgh, Western General Hospital
Timothy D. Spector: King’s College London
James F. Wilson: University of Edinburgh
Gordan Lauc: Genos Glycoscience Research Laboratory
Yurii S. Aulchenko: Novosibirsk State University

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-00453-3

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