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Defining the genetic control of human blood plasma N-glycome using genome-wide association study. / Sharapov, Sodbo Zh; Tsepilov, Yakov A.; Klaric, Lucija et al.

In: Human Molecular Genetics, Vol. 28, No. 12, 15.06.2019, p. 2062-2077.

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

Harvard

Sharapov, SZ, Tsepilov, YA, Klaric, L, Mangino, M, Thareja, G, Shadrina, AS, Simurina, M, Dagostino, C, Dmitrieva, J, Vilaj, M, Vuckovic, F, Pavic, T, Stambuk, J, Trbojevic-Akmacic, I, Kristic, J, Simunovic, J, Momcilovic, A, Campbell, H, Doherty, M, Dunlop, MG, Farrington, SM, Pucic-Bakovic, M, Gieger, C, Allegri, M, Louis, E, Georges, M, Suhre, K, Spector, T, Williams, FMK, Lauc, G & Aulchenko, YS 2019, 'Defining the genetic control of human blood plasma N-glycome using genome-wide association study', Human Molecular Genetics, vol. 28, no. 12, pp. 2062-2077. https://doi.org/10.1093/hmg/ddz054

APA

Sharapov, S. Z., Tsepilov, Y. A., Klaric, L., Mangino, M., Thareja, G., Shadrina, A. S., Simurina, M., Dagostino, C., Dmitrieva, J., Vilaj, M., Vuckovic, F., Pavic, T., Stambuk, J., Trbojevic-Akmacic, I., Kristic, J., Simunovic, J., Momcilovic, A., Campbell, H., Doherty, M., ... Aulchenko, Y. S. (2019). Defining the genetic control of human blood plasma N-glycome using genome-wide association study. Human Molecular Genetics, 28(12), 2062-2077. https://doi.org/10.1093/hmg/ddz054

Vancouver

Sharapov SZ, Tsepilov YA, Klaric L, Mangino M, Thareja G, Shadrina AS et al. Defining the genetic control of human blood plasma N-glycome using genome-wide association study. Human Molecular Genetics. 2019 Jun 15;28(12):2062-2077. doi: 10.1093/hmg/ddz054

Author

Sharapov, Sodbo Zh ; Tsepilov, Yakov A. ; Klaric, Lucija et al. / Defining the genetic control of human blood plasma N-glycome using genome-wide association study. In: Human Molecular Genetics. 2019 ; Vol. 28, No. 12. pp. 2062-2077.

BibTeX

@article{de1835df2c5e4e76bdd599fe7ffcf0ad,
title = "Defining the genetic control of human blood plasma N-glycome using genome-wide association study",
abstract = "Glycosylation is a common post-translational modification of proteins. Glycosylation is associated with a number of human diseases. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people measured by Ultra Performance Liquid Chromatography (UPLC) technology. Starting with the 36 original traits measured by UPLC, we computed an additional 77 derived traits leading to a total of 113 glycan traits. We studied associations between these traits and genetic polymorphisms located on human autosomes. We discovered and replicated 12 loci. This allowed us to demonstrate an overlap in genetic control between total plasma protein and IgG glycosylation. The majority of revealed loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3 and MGAT5) and a known regulator of plasma protein fucosylation (HNF1A). However, we also found loci that could possibly reflect other more complex aspects of glycosylation process. Functional genomic annotation suggested the role of several genes including DERL3, CHCHD10, TMEM121, IGH and IKZF1. The hypotheses we generated may serve as a starting point for further functional studies in this research area.",
keywords = "Chromatography, High Pressure Liquid, Cohort Studies, Fucosyltransferases/blood, Genome-Wide Association Study, Glucuronosyltransferase/blood, Glycosylation, Glycosyltransferases/genetics, Hepatocyte Nuclear Factor 1-alpha/blood, Humans, Immunoglobulin G/metabolism, Membrane Proteins/metabolism, Polymorphism, Genetic, Polysaccharides/blood, Quantitative Trait Loci",
author = "Sharapov, {Sodbo Zh} and Tsepilov, {Yakov A.} and Lucija Klaric and Massimo Mangino and Gaurav Thareja and Shadrina, {Alexandra S.} and Mirna Simurina and Concetta Dagostino and Julia Dmitrieva and Marija Vilaj and Frano Vuckovic and Tamara Pavic and Jerko Stambuk and Irena Trbojevic-Akmacic and Jasminka Kristic and Jelena Simunovic and Ana Momcilovic and Harry Campbell and Margaret Doherty and Dunlop, {Malcolm G.} and Farrington, {Susan M.} and Maja Pucic-Bakovic and Christian Gieger and Massimo Allegri and Edouard Louis and Michel Georges and Karsten Suhre and Tim Spector and Williams, {Frances M.K.} and Gordan Lauc and Aulchenko, {Yurii S.}",
note = "Publisher Copyright: {\textcopyright} The Author(s) 2019.",
year = "2019",
month = jun,
day = "15",
doi = "10.1093/hmg/ddz054",
language = "English",
volume = "28",
pages = "2062--2077",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "12",

}

RIS

TY - JOUR

T1 - Defining the genetic control of human blood plasma N-glycome using genome-wide association study

AU - Sharapov, Sodbo Zh

AU - Tsepilov, Yakov A.

AU - Klaric, Lucija

AU - Mangino, Massimo

AU - Thareja, Gaurav

AU - Shadrina, Alexandra S.

AU - Simurina, Mirna

AU - Dagostino, Concetta

AU - Dmitrieva, Julia

AU - Vilaj, Marija

AU - Vuckovic, Frano

AU - Pavic, Tamara

AU - Stambuk, Jerko

AU - Trbojevic-Akmacic, Irena

AU - Kristic, Jasminka

AU - Simunovic, Jelena

AU - Momcilovic, Ana

AU - Campbell, Harry

AU - Doherty, Margaret

AU - Dunlop, Malcolm G.

AU - Farrington, Susan M.

AU - Pucic-Bakovic, Maja

AU - Gieger, Christian

AU - Allegri, Massimo

AU - Louis, Edouard

AU - Georges, Michel

AU - Suhre, Karsten

AU - Spector, Tim

AU - Williams, Frances M.K.

AU - Lauc, Gordan

AU - Aulchenko, Yurii S.

N1 - Publisher Copyright: © The Author(s) 2019.

PY - 2019/6/15

Y1 - 2019/6/15

N2 - Glycosylation is a common post-translational modification of proteins. Glycosylation is associated with a number of human diseases. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people measured by Ultra Performance Liquid Chromatography (UPLC) technology. Starting with the 36 original traits measured by UPLC, we computed an additional 77 derived traits leading to a total of 113 glycan traits. We studied associations between these traits and genetic polymorphisms located on human autosomes. We discovered and replicated 12 loci. This allowed us to demonstrate an overlap in genetic control between total plasma protein and IgG glycosylation. The majority of revealed loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3 and MGAT5) and a known regulator of plasma protein fucosylation (HNF1A). However, we also found loci that could possibly reflect other more complex aspects of glycosylation process. Functional genomic annotation suggested the role of several genes including DERL3, CHCHD10, TMEM121, IGH and IKZF1. The hypotheses we generated may serve as a starting point for further functional studies in this research area.

AB - Glycosylation is a common post-translational modification of proteins. Glycosylation is associated with a number of human diseases. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people measured by Ultra Performance Liquid Chromatography (UPLC) technology. Starting with the 36 original traits measured by UPLC, we computed an additional 77 derived traits leading to a total of 113 glycan traits. We studied associations between these traits and genetic polymorphisms located on human autosomes. We discovered and replicated 12 loci. This allowed us to demonstrate an overlap in genetic control between total plasma protein and IgG glycosylation. The majority of revealed loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3 and MGAT5) and a known regulator of plasma protein fucosylation (HNF1A). However, we also found loci that could possibly reflect other more complex aspects of glycosylation process. Functional genomic annotation suggested the role of several genes including DERL3, CHCHD10, TMEM121, IGH and IKZF1. The hypotheses we generated may serve as a starting point for further functional studies in this research area.

KW - Chromatography, High Pressure Liquid

KW - Cohort Studies

KW - Fucosyltransferases/blood

KW - Genome-Wide Association Study

KW - Glucuronosyltransferase/blood

KW - Glycosylation

KW - Glycosyltransferases/genetics

KW - Hepatocyte Nuclear Factor 1-alpha/blood

KW - Humans

KW - Immunoglobulin G/metabolism

KW - Membrane Proteins/metabolism

KW - Polymorphism, Genetic

KW - Polysaccharides/blood

KW - Quantitative Trait Loci

UR - http://www.scopus.com/inward/record.url?scp=85067482457&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddz054

DO - 10.1093/hmg/ddz054

M3 - Article

C2 - 31163085

AN - SCOPUS:85067482457

VL - 28

SP - 2062

EP - 2077

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 12

ER -

ID: 26207867