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
Y1 - 2019
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.
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
SN - 0964-6906
VL - 28
SP - 2062
EP - 2077
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 12
ER -
