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

Sodbo Zh Sharapov, Yakov A Tsepilov, Lucija Klaric, Massimo Mangino, Guarav Thareja, Alexandra S. Shadrina, Mirna Šimurina, Concetta Dagostino, Julia Dmitrieva, Marija Vilaj, Frano Vuckovic, Tamara Pavic, Jerko Stambuk, Irena Trbojevic-Akmacic, Jasminka Kristic, Jelena Simunovic, Ana Momcilovic, Harry Campbell, Margaret Doherty, Malcolm DunlopSusan Farrington, Maja Pucic Bakovic, Christian Gieger, Massimo Allegri, Edouard Louis, Michel Georges, Karsten Suhre, Timothy D. Spector, Frances M. K. Williams, G. Lauc, Yurii Aulchenko

Research output: Contribution to journalArticlepeer-review


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 3,811 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 twelve 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.
Original languageEnglish
Pages (from-to)2062-2077
Number of pages16
JournalHuman Molecular Genetics
Issue number12
Publication statusPublished - 11 Mar 2019


  • 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


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