TY - CHAP

T1 - Quantitative Genetics of Human Protein N-Glycosylation

AU - Krištić, Jasminka

AU - Sharapov, Sodbo Zh

AU - Aulchenko, Yurii S.

N1 - Funding Information: Funding The work of SZS and YSA was supported by a grant from Russian Science Foundation (RSF) No. 19-15-00115. The work of JK was supported by European Structural and Investment Funds CEKOM grant (#KK.01.2.2.03.0006) and Croatian National Centre of Research Excellence in Personalized Healthcare grant (#KK.01.1.1.01.0010). Publisher Copyright: © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.

PY - 2021

Y1 - 2021

N2 - Although changes in protein glycosylation are observed in a wide range of diseases and pathological states, the examples of use of glycans as biomarkers and therapeutic targets are limited. This is not in small part because the understanding of human glycome regulation in vivo is incomplete and fragmented. Combination of human glycomics and genomics offers a powerful “data-driven hypotheses” approach to dissect the complex human glycobiology in vivo in an agnostic manner. In this chapter we review a decade of quantitative genetic studies of human N-glycome, including studies of its heritability and gene-mapping via genome-wide association studies (GWASs). We show that GWASs of human N-glycome start revealing regulators of the biochemical network of N-glycosylation. Some of these regulators demonstrate pleiotropic effects on human disease, especially autoimmune and inflammatory. We emphasize the use of in silico functional methods and multi-omics approaches to prioritize functional mechanisms to be further validated in laboratory experiments. This combined approach will lead to better understanding of mechanisms of regulation of human protein glycosylation and will provide a rich source of etiologic insight, therapeutic interventions, and biomarkers.

AB - Although changes in protein glycosylation are observed in a wide range of diseases and pathological states, the examples of use of glycans as biomarkers and therapeutic targets are limited. This is not in small part because the understanding of human glycome regulation in vivo is incomplete and fragmented. Combination of human glycomics and genomics offers a powerful “data-driven hypotheses” approach to dissect the complex human glycobiology in vivo in an agnostic manner. In this chapter we review a decade of quantitative genetic studies of human N-glycome, including studies of its heritability and gene-mapping via genome-wide association studies (GWASs). We show that GWASs of human N-glycome start revealing regulators of the biochemical network of N-glycosylation. Some of these regulators demonstrate pleiotropic effects on human disease, especially autoimmune and inflammatory. We emphasize the use of in silico functional methods and multi-omics approaches to prioritize functional mechanisms to be further validated in laboratory experiments. This combined approach will lead to better understanding of mechanisms of regulation of human protein glycosylation and will provide a rich source of etiologic insight, therapeutic interventions, and biomarkers.

KW - Genetic regulation

KW - Genome-wide association

KW - Glycomics

KW - Glycoproteins

KW - Heritability

KW - N-glycosylation

KW - Genome-Wide Association Study

KW - Polysaccharides

KW - Genomics

KW - Humans

KW - Glycosylation

UR - http://www.scopus.com/inward/record.url?scp=85115018541&partnerID=8YFLogxK

UR - https://www.elibrary.ru/item.asp?id=47064073

UR - https://www.mendeley.com/catalogue/463384d4-d21a-37b4-b34a-7a39f557f311/

U2 - 10.1007/978-3-030-70115-4_7

DO - 10.1007/978-3-030-70115-4_7

M3 - Chapter

C2 - 34495534

AN - SCOPUS:85115018541

SN - 978-3-030-70114-7

SN - 978-3-030-70117-8

VL - 1325

T3 - Advances in Experimental Medicine and Biology

SP - 151

EP - 171

BT - Advances in Experimental Medicine and Biology

A2 - Lauc, Gordan

A2 - Trbojević-Akmačić, Irena

PB - Springer, Cham

ER -