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

Результат исследования: Научные публикации в периодических изданияхстатья

19 Цитирования (Scopus)

Аннотация

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.

Язык оригиналаанглийский
Номер статьи447
Страницы (с-по)447
Число страниц10
ЖурналNature Communications
Том8
Номер выпуска1
DOI
СостояниеОпубликовано - 6 сен 2017

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