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

doi:10.1038/s41467-017-00453-3

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 journal › Article › peer-review

28 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 language	English
Article number	447
Pages (from-to)	447
Number of pages	10
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00453-3
Publication status	Published - 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

Access to Document

10.1038/s41467-017-00453-3

Cite this

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

@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",

}

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

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.

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 -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this