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Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation
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Number of Authors: 152017 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 8, article id 447Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2017. Vol. 8, article id 447
National Category
Medical Genetics and Genomics
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URN: urn:nbn:se:su:diva-180166DOI: 10.1038/s41467-017-00453-3ISI: 000409458000001PubMedID: 28878392OAI: oai:DiVA.org:su-180166DiVA, id: diva2:1415710
Available from: 2020-03-19 Created: 2020-03-19 Last updated: 2025-02-10Bibliographically approved

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Shen, XiaKlarić, LucijaSharapov, SodboWu, DiAulchenko, Yurii S.

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