Investigation of the causal relationships between human IgG N-glycosylation and 12 common diseases associated with changes in the IgG N-glycome

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Investigation of the causal relationships between human IgG N-glycosylation and 12 common diseases associated with changes in the IgG N-glycome. / Zaytseva, Olga O.; Sharapov, Sodbo Zh; Perola, Marcus et al.

In: Human Molecular Genetics, Vol. 31, No. 10, 15.05.2022, p. 1545-1559.

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

BibTeX

@article{a3964f2cdc7b466fac8784a374a36d4a,

title = "Investigation of the causal relationships between human IgG N-glycosylation and 12 common diseases associated with changes in the IgG N-glycome",

abstract = "Changes in the N-glycosylation of immunoglobulin G (IgG) are often observed in pathological states, such as autoimmune, inflammatory, neurodegenerative, cardiovascular diseases and some types of cancer. However, in most cases, it is not clear if the disease onset causes these changes, or if the changes in IgG N-glycosylation are among the risk factors for the diseases. The aim of this study was to investigate the casual relationships between IgG N-glycosylation traits and 12 diseases, in which the alterations of IgG N-glycome were previously reported, using two sample Mendelian randomization (MR) approach. We have performed two sample MR using publicly available summary statistics of genome-wide association studies of IgG N-glycosylation and disease risks. Our results indicate positive causal effect of systemic lupus erythematosus (SLE) on the abundance of N-glycans with bisecting N-acetylglucosamine in the total IgG N-glycome. Therefore, we suggest regarding this IgG glycosylation trait as a biomarker of SLE. We also emphasize the need for more powerful GWAS studies of IgG N-glycosylation to further elucidate the causal effect of IgG N-glycome on the diseases.",

keywords = "Genome-Wide Association Study, Glycosylation, Humans, Immunoglobulin G/genetics, Lupus Erythematosus, Systemic/genetics, Polysaccharides/genetics",

author = "Zaytseva, {Olga O.} and Sharapov, {Sodbo Zh} and Marcus Perola and Tonu Esko and Arianna Landini and Caroline Hayward and Wilson, {James F.} and Gordan Lauc and Aulchenko, {Yurii S.} and Lucija Klari{\'c} and Tsepilov, {Yakov A.}",

year = "2022",

month = may,

day = "15",

doi = "10.1093/hmg/ddab335",

language = "English",

volume = "31",

pages = "1545--1559",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "10",

}

RIS

TY - JOUR

T1 - Investigation of the causal relationships between human IgG N-glycosylation and 12 common diseases associated with changes in the IgG N-glycome

AU - Zaytseva, Olga O.

AU - Sharapov, Sodbo Zh

AU - Perola, Marcus

AU - Esko, Tonu

AU - Landini, Arianna

AU - Hayward, Caroline

AU - Wilson, James F.

AU - Lauc, Gordan

AU - Aulchenko, Yurii S.

AU - Klarić, Lucija

AU - Tsepilov, Yakov A.

PY - 2022/5/15

Y1 - 2022/5/15

N2 - Changes in the N-glycosylation of immunoglobulin G (IgG) are often observed in pathological states, such as autoimmune, inflammatory, neurodegenerative, cardiovascular diseases and some types of cancer. However, in most cases, it is not clear if the disease onset causes these changes, or if the changes in IgG N-glycosylation are among the risk factors for the diseases. The aim of this study was to investigate the casual relationships between IgG N-glycosylation traits and 12 diseases, in which the alterations of IgG N-glycome were previously reported, using two sample Mendelian randomization (MR) approach. We have performed two sample MR using publicly available summary statistics of genome-wide association studies of IgG N-glycosylation and disease risks. Our results indicate positive causal effect of systemic lupus erythematosus (SLE) on the abundance of N-glycans with bisecting N-acetylglucosamine in the total IgG N-glycome. Therefore, we suggest regarding this IgG glycosylation trait as a biomarker of SLE. We also emphasize the need for more powerful GWAS studies of IgG N-glycosylation to further elucidate the causal effect of IgG N-glycome on the diseases.

AB - Changes in the N-glycosylation of immunoglobulin G (IgG) are often observed in pathological states, such as autoimmune, inflammatory, neurodegenerative, cardiovascular diseases and some types of cancer. However, in most cases, it is not clear if the disease onset causes these changes, or if the changes in IgG N-glycosylation are among the risk factors for the diseases. The aim of this study was to investigate the casual relationships between IgG N-glycosylation traits and 12 diseases, in which the alterations of IgG N-glycome were previously reported, using two sample Mendelian randomization (MR) approach. We have performed two sample MR using publicly available summary statistics of genome-wide association studies of IgG N-glycosylation and disease risks. Our results indicate positive causal effect of systemic lupus erythematosus (SLE) on the abundance of N-glycans with bisecting N-acetylglucosamine in the total IgG N-glycome. Therefore, we suggest regarding this IgG glycosylation trait as a biomarker of SLE. We also emphasize the need for more powerful GWAS studies of IgG N-glycosylation to further elucidate the causal effect of IgG N-glycome on the diseases.

KW - Genome-Wide Association Study

KW - Glycosylation

KW - Humans

KW - Immunoglobulin G/genetics

KW - Lupus Erythematosus, Systemic/genetics

KW - Polysaccharides/genetics

UR - http://www.scopus.com/inward/record.url?scp=85128789503&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddab335

DO - 10.1093/hmg/ddab335

M3 - Article

C2 - 34791244

AN - SCOPUS:85128789503

VL - 31

SP - 1545

EP - 1559

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 10

ER -

ID: 36201966