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Nat Commun. 2017 Sep 6;8(1):447. doi: 10.1038/s41467-017-00453-3.

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

Author information

1
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK. xia.shen@ed.ac.uk.
2
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12 A, SE-17 177, Stockholm, Sweden. xia.shen@ed.ac.uk.
3
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crew Road, Edinburgh, EH4 2XU, Scotland, UK. xia.shen@ed.ac.uk.
4
Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, UK.
5
MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Crew Road, Edinburgh, EH4 2XU, Scotland, UK.
6
Genos Glycoscience Research Laboratory, Hondlova 2/11, Zagreb, 10000, Croatia.
7
Novosibirsk State University, Pirogova 2, Novosibirsk, 630090, Russia.
8
Institute of Cytology and Genetics SB RAS, Lavrentyeva ave. 10, Novosibirsk, 630090, Russia.
9
Department for Twin Research, King's College London, London, WC2R 2LS, England, UK.
10
National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St. Thomas' Foundation Trust, London, SE1 9RT, England, UK.
11
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels väg 12 A, SE-17 177, Stockholm, Sweden.
12
Science for Life Laboratory, Department of Biochemistry and Biophysics, Stockholm University, Tomtebodavägen 23B, Stockholm, SE-171 65, Sweden.
13
Faculty of Medicine, University of Split, Šoltanska ul. 2, Split, 21000, Croatia.
14
Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacica 1, Zagreb, 10000, Croatia.
15
Novosibirsk State University, Pirogova 2, Novosibirsk, 630090, Russia. y.s.aulchenko@polyomica.com.
16
Institute of Cytology and Genetics SB RAS, Lavrentyeva ave. 10, Novosibirsk, 630090, Russia. y.s.aulchenko@polyomica.com.
17
PolyOmica, Het Vlaggeschip 61, 's-Hertogenbosch, 5237PA, The Netherlands. y.s.aulchenko@polyomica.com.

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.Multivariate analysis methods can uncover the relationship between phenotypic measures characterised by modern omic techniques. Here the authors conduct a multivariate GWAS on IgG N-glycosylation phenotypes and identify 5 novel loci enriched in immune system genes.

PMID:
28878392
PMCID:
PMC5587582
DOI:
10.1038/s41467-017-00453-3
[Indexed for MEDLINE]
Free PMC Article

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