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, Yurii S. Aulchenko

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Article number447
Pages (from-to)447
Number of pages10
JournalNature Communications
Volume8
Issue number1
DOIs
Publication statusPublished - 6 Sep 2017

Keywords

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes/metabolism
  • Cell Cycle Proteins/genetics
  • Cohort Studies
  • Female
  • Fucosyltransferases/genetics
  • Genetic Loci
  • Genetic Pleiotropy
  • Genome-Wide Association Study
  • Glycosylation
  • Humans
  • Immunoglobulin G/genetics
  • Male
  • Microtubule Proteins/genetics
  • Middle Aged
  • Phenotype
  • Transcriptional Elongation Factors/genetics
  • United Kingdom
  • Young Adult
  • SET
  • MIXED-MODEL
  • TRAITS
  • GENOME-WIDE ASSOCIATION
  • IGG
  • DISEASE

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