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Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation. / Shen, Xia; Klarić, Lucija; Sharapov, Sodbo et al.

In: Nature Communications, Vol. 8, No. 1, 447, 06.09.2017, p. 447.

Research output: Contribution to journal › Article › peer-review

Harvard

Shen, X, Klarić, L, Sharapov, S, Mangino, M, Ning, Z, Wu, D, Trbojević-Akmačić, I, Pučić-Baković, M, Rudan, I, Polašek, O, Hayward, C, Spector, TD, Wilson, JF, Lauc, G & Aulchenko, YS 2017, 'Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation', Nature Communications, vol. 8, no. 1, 447, pp. 447. https://doi.org/10.1038/s41467-017-00453-3

APA

Shen, X., Klarić, L., Sharapov, S., Mangino, M., Ning, Z., Wu, D., Trbojević-Akmačić, I., Pučić-Baković, M., Rudan, I., Polašek, O., Hayward, C., Spector, T. D., Wilson, J. F., Lauc, G., & Aulchenko, Y. S. (2017). Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation. Nature Communications, 8(1), 447. [447]. https://doi.org/10.1038/s41467-017-00453-3

Vancouver

Shen X, Klarić L, Sharapov S, Mangino M, Ning Z, Wu D et al. Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation. Nature Communications. 2017 Sept 6;8(1):447. 447. doi: 10.1038/s41467-017-00453-3

Author

Shen, Xia ; Klarić, Lucija ; Sharapov, Sodbo et al. / Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation. In: Nature Communications. 2017 ; Vol. 8, No. 1. pp. 447.

BibTeX

@article{07fd94a7b6fb44f88b86309fa257afe5,
title = "Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation",
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.",
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",
author = "Xia Shen and Lucija Klari{\'c} and Sodbo Sharapov and Massimo Mangino and Zheng Ning and Di Wu and Irena Trbojevi{\'c}-Akma{\v c}i{\'c} and Maja Pu{\v c}i{\'c}-Bakovi{\'c} and Igor Rudan and Ozren Pola{\v s}ek and Caroline Hayward and Spector, {Timothy D.} and Wilson, {James F.} and Gordan Lauc and Aulchenko, {Yurii S.}",
note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",
year = "2017",
month = sep,
day = "6",
doi = "10.1038/s41467-017-00453-3",
language = "English",
volume = "8",
pages = "447",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation

AU - Shen, Xia

AU - Klarić, Lucija

AU - Sharapov, Sodbo

AU - Mangino, Massimo

AU - Ning, Zheng

AU - Wu, Di

AU - Trbojević-Akmačić, Irena

AU - Pučić-Baković, Maja

AU - Rudan, Igor

AU - Polašek, Ozren

AU - Hayward, Caroline

AU - Spector, Timothy D.

AU - Wilson, James F.

AU - Lauc, Gordan

AU - Aulchenko, Yurii S.

N1 - Publisher Copyright: © 2017 The Author(s).

PY - 2017/9/6

Y1 - 2017/9/6

N2 - 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.

AB - 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.

KW - Adolescent

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - B-Lymphocytes/metabolism

KW - Cell Cycle Proteins/genetics

KW - Cohort Studies

KW - Female

KW - Fucosyltransferases/genetics

KW - Genetic Loci

KW - Genetic Pleiotropy

KW - Genome-Wide Association Study

KW - Glycosylation

KW - Humans

KW - Immunoglobulin G/genetics

KW - Male

KW - Microtubule Proteins/genetics

KW - Middle Aged

KW - Phenotype

KW - Transcriptional Elongation Factors/genetics

KW - United Kingdom

KW - Young Adult

KW - SET

KW - MIXED-MODEL

KW - TRAITS

KW - GENOME-WIDE ASSOCIATION

KW - IGG

KW - DISEASE

UR - http://www.scopus.com/inward/record.url?scp=85028950118&partnerID=8YFLogxK

U2 - 10.1038/s41467-017-00453-3

DO - 10.1038/s41467-017-00453-3

M3 - Article

C2 - 28878392

AN - SCOPUS:85028950118

VL - 8

SP - 447

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 447

ER -

ID: 9866820