Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Multivariate discovery and replication of five novel loci associated with Immunoglobulin G N-glycosylation. / Shen, Xia; Klarić, Lucija; Sharapov, Sodbo и др.
в: Nature Communications, Том 8, № 1, 447, 06.09.2017, стр. 447.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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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.
N1 - Publisher Copyright: © 2017 The Author(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 -
ID: 9866820