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 Polasek; Caroline Hayward; Tim 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 Polasek, Caroline Hayward, Tim D Spector, James F. Wilson, Gordan Lauc, Yurii S. Aulchenko

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

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
Number of pages	10
Journal	Nature Communications
Volume	8
DOIs	https://doi.org/10.1038/s41467-017-00453-3
Publication status	Published - 6 Sept 2017

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Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylationFinal published version, 1.41 MBLicence: Creative Commons: Attribution (CC-BY)

Genome-wide p-values of nine multivariate IgG glycan GWAS
Shen, X. (Creator), Edinburgh DataShare, 16 Jun 2017
DOI: 10.7488/ds/2069
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Shen, X., Klarić, L., Sharapov, S., Mangino, M., Ning, Z., Wu, D., Trbojević-Akmačić, I., Pučić-Baković, M., Rudan, I., Polasek, 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, Article 447. https://doi.org/10.1038/s41467-017-00453-3

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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.",

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 Polasek and Caroline Hayward and Spector, \{Tim D\} and Wilson, \{James F.\} and Gordan Lauc and Aulchenko, \{Yurii S.\}",

year = "2017",

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day = "6",

doi = "10.1038/s41467-017-00453-3",

language = "English",

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Shen, X, Klarić, L, Sharapov, S, Mangino, M, Ning, Z, Wu, D, Trbojević-Akmačić, I, Pučić-Baković, M, Rudan, I, Polasek, 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, 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 - Polasek, Ozren

AU - Hayward, Caroline

AU - Spector, Tim 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.

U2 - 10.1038/s41467-017-00453-3

DO - 10.1038/s41467-017-00453-3

M3 - Article

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 447

ER -

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

Abstract

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Genome-wide p-values of nine multivariate IgG glycan GWAS

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