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, w...

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Vydáno v:Nature communications Ročník 8; číslo 1; s. 447 - 10
Hlavní autoři: 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.
Médium: Journal Article
Jazyk:angličtina
Vydáno: London Nature Publishing Group UK 06.09.2017
Nature Publishing Group
Nature Portfolio
Témata:
631/114/2163
631/208/205/2138
Adolescent
Adult
Aged
Aged, 80 and over
B-Lymphocytes - metabolism
Cell Cycle Proteins - genetics
Cohort Studies
Cytoskeletal Proteins
Female
Fucosyltransferases - genetics
Genetic Loci
Genetic Pleiotropy
Genome-wide association studies
Genome-Wide Association Study
Glycosylation
Humanities and Social Sciences
Humans
Immune system
Immunoglobulin G
Immunoglobulin G - genetics
Immunoglobulin G - metabolism
Loci
Lymphocytes
Male
Microtubule Proteins - genetics
Middle Aged
multidisciplinary
Multivariate analysis
Phenotype
Science
Science (multidisciplinary)
Transcriptional Elongation Factors - genetics
United Kingdom
Young Adult
United Kingdom
ISSN:2041-1723, 2041-1723
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Popis
Shrnutí: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. Multivariate analysis methods can uncover the relationship between phenotypic measures characterised by modern omic techniques. Here the authors conduct a multivariate GWAS on IgG N -glycosylation phenotypes and identify 5 novel loci enriched in immune system genes.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-00453-3