Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Multivariate genome-wide analysis of immunoglobulin G N-glycosylation identifies new loci pleiotropic with immune function. / Shadrina, Alexandra S.; Zlobin, Alexander S.; Zaytseva, Olga O. и др.
в: Human Molecular Genetics, Том 30, № 13, 01.07.2021, стр. 1259-1270.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Multivariate genome-wide analysis of immunoglobulin G N-glycosylation identifies new loci pleiotropic with immune function
AU - Shadrina, Alexandra S.
AU - Zlobin, Alexander S.
AU - Zaytseva, Olga O.
AU - Klarić, Lucija
AU - Sharapov, Sodbo Z.
AU - D Pakhomov, Eugene
AU - Perola, Marcus
AU - Esko, Tonu
AU - Hayward, Caroline
AU - Wilson, James F.
AU - Lauc, Gordan
AU - Aulchenko, Yurii S.
AU - Tsepilov, Yakov A.
N1 - Publisher Copyright: © 2021 The Author(s). Published by Oxford University Press. All rights reserved. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7/1
Y1 - 2021/7/1
N2 - The N-glycosylation of immunoglobulin G (IgG) affects its structure and function. It has been demonstrated that IgG N-glycosylation patterns are inherited as complex quantitative traits. Genome-wide association studies identified loci harboring genes encoding enzymes directly involved in protein glycosylation as well as loci likely to be involved in regulation of glycosylation biochemical pathways. Many of these loci could be linked to immune functions and risk of inflammatory and autoimmune diseases. The aim of the present study was to discover and replicate new loci associated with IgG N-glycosylation and to investigate possible pleiotropic effects of these loci onto immune function and the risk of inflammatory and autoimmune diseases. We conducted a multivariate genome-wide association analysis of 23 IgG N-glycosylation traits measured in 8090 individuals of European ancestry. The discovery stage was followed up by replication in 3147 people and in silico functional analysis. Our study increased the total number of replicated loci from 22 to 29. For the discovered loci, we suggest a number of genes potentially involved in the control of IgG N-glycosylation. Among the new loci, two (near RNF168 and TNFRSF13B) were previously implicated in rare immune deficiencies and were associated with levels of circulating immunoglobulins. For one new locus (near AP5B1/OVOL1), we demonstrated a potential pleiotropic effect on the risk of asthma. Our findings underline an important link between IgG N-glycosylation and immune function and provide new clues to understanding their interplay.
AB - The N-glycosylation of immunoglobulin G (IgG) affects its structure and function. It has been demonstrated that IgG N-glycosylation patterns are inherited as complex quantitative traits. Genome-wide association studies identified loci harboring genes encoding enzymes directly involved in protein glycosylation as well as loci likely to be involved in regulation of glycosylation biochemical pathways. Many of these loci could be linked to immune functions and risk of inflammatory and autoimmune diseases. The aim of the present study was to discover and replicate new loci associated with IgG N-glycosylation and to investigate possible pleiotropic effects of these loci onto immune function and the risk of inflammatory and autoimmune diseases. We conducted a multivariate genome-wide association analysis of 23 IgG N-glycosylation traits measured in 8090 individuals of European ancestry. The discovery stage was followed up by replication in 3147 people and in silico functional analysis. Our study increased the total number of replicated loci from 22 to 29. For the discovered loci, we suggest a number of genes potentially involved in the control of IgG N-glycosylation. Among the new loci, two (near RNF168 and TNFRSF13B) were previously implicated in rare immune deficiencies and were associated with levels of circulating immunoglobulins. For one new locus (near AP5B1/OVOL1), we demonstrated a potential pleiotropic effect on the risk of asthma. Our findings underline an important link between IgG N-glycosylation and immune function and provide new clues to understanding their interplay.
UR - http://www.scopus.com/inward/record.url?scp=85108741844&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddab072
DO - 10.1093/hmg/ddab072
M3 - Article
C2 - 33710309
AN - SCOPUS:85108741844
VL - 30
SP - 1259
EP - 1270
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 13
ER -
ID: 29137258