Multivariate genome-wide analysis of immunoglobulin G N-glycosylation identifies new loci pleiotropic with immune function

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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. et al.

In: Human Molecular Genetics, Vol. 30, No. 13, 01.07.2021, p. 1259-1270.

Research output: Contribution to journal › Article › peer-review

Harvard

Shadrina, AS, Zlobin, AS, Zaytseva, OO, Klarić, L, Sharapov, SZ, D Pakhomov, E, Perola, M, Esko, T, Hayward, C, Wilson, JF, Lauc, G, Aulchenko, YS & Tsepilov, YA 2021, 'Multivariate genome-wide analysis of immunoglobulin G N-glycosylation identifies new loci pleiotropic with immune function', Human Molecular Genetics, vol. 30, no. 13, pp. 1259-1270. https://doi.org/10.1093/hmg/ddab072

APA

Shadrina, A. S., Zlobin, A. S., Zaytseva, O. O., Klarić, L., Sharapov, S. Z., D Pakhomov, E., Perola, M., Esko, T., Hayward, C., Wilson, J. F., Lauc, G., Aulchenko, Y. S., & Tsepilov, Y. A. (2021). Multivariate genome-wide analysis of immunoglobulin G N-glycosylation identifies new loci pleiotropic with immune function. Human Molecular Genetics, 30(13), 1259-1270. https://doi.org/10.1093/hmg/ddab072

Vancouver

Shadrina AS, Zlobin AS, Zaytseva OO, Klarić L, Sharapov SZ, D Pakhomov E et al. Multivariate genome-wide analysis of immunoglobulin G N-glycosylation identifies new loci pleiotropic with immune function. Human Molecular Genetics. 2021 Jul 1;30(13):1259-1270. doi: 10.1093/hmg/ddab072

Author

Shadrina, Alexandra S. ; Zlobin, Alexander S. ; Zaytseva, Olga O. et al. / Multivariate genome-wide analysis of immunoglobulin G N-glycosylation identifies new loci pleiotropic with immune function. In: Human Molecular Genetics. 2021 ; Vol. 30, No. 13. pp. 1259-1270.

BibTeX

@article{66353f16b63d49a9a84ecd02ff0575c7,

title = "Multivariate genome-wide analysis of immunoglobulin G N-glycosylation identifies new loci pleiotropic with immune function",

abstract = "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. ",

author = "Shadrina, {Alexandra S.} and Zlobin, {Alexander S.} and Zaytseva, {Olga O.} and Lucija Klari{\'c} and Sharapov, {Sodbo Z.} and {D Pakhomov}, Eugene and Marcus Perola and Tonu Esko and Caroline Hayward and Wilson, {James F.} and Gordan Lauc and Aulchenko, {Yurii S.} and Tsepilov, {Yakov A.}",

year = "2021",

month = jul,

day = "1",

doi = "10.1093/hmg/ddab072",

language = "English",

volume = "30",

pages = "1259--1270",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "13",

}

RIS

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.

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