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

Author

Listed:
  • Xia Shen

    (University of Edinburgh
    Karolinska Institutet
    University of Edinburgh, Western General Hospital)

  • Lucija Klarić

    (University of Edinburgh
    University of Edinburgh, Western General Hospital
    Genos Glycoscience Research Laboratory)

  • Sodbo Sharapov

    (Novosibirsk State University
    Institute of Cytology and Genetics SB RAS)

  • Massimo Mangino

    (King’s College London
    National Institute for Health Research (NIHR) Biomedical Research Centre at Guy’s and St. Thomas’ Foundation Trust)

  • Zheng Ning

    (Karolinska Institutet)

  • Di Wu

    (Stockholm University)

  • Irena Trbojević-Akmačić

    (Genos Glycoscience Research Laboratory)

  • Maja Pučić-Baković

    (Genos Glycoscience Research Laboratory)

  • Igor Rudan

    (University of Edinburgh
    University of Edinburgh, Western General Hospital)

  • Ozren Polašek

    (University of Split)

  • Caroline Hayward

    (University of Edinburgh, Western General Hospital)

  • Timothy D. Spector

    (King’s College London)

  • James F. Wilson

    (University of Edinburgh
    University of Edinburgh, Western General Hospital)

  • Gordan Lauc

    (Genos Glycoscience Research Laboratory
    University of Zagreb)

  • Yurii S. Aulchenko

    (Novosibirsk State University
    Institute of Cytology and Genetics SB RAS
    PolyOmica, Het Vlaggeschip 61)

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.

Suggested Citation

  • 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 & J, 2017. "Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00453-3
    DOI: 10.1038/s41467-017-00453-3
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    Cited by:

    1. Xinyuan Zhang & Anastasia M. Lucas & Yogasudha Veturi & Theodore G. Drivas & William P. Bone & Anurag Verma & Wendy K. Chung & David Crosslin & Joshua C. Denny & Scott Hebbring & Gail P. Jarvik & Ifti, 2022. "Large-scale genomic analyses reveal insights into pleiotropy across circulatory system diseases and nervous system disorders," Nature Communications, Nature, vol. 13(1), pages 1-12, December.

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