Accepted_test

A genome-wide association study of the plasma N-glycome in 10,000 individuals identifies 16 novel loci and highlights glycan-associated human traits
by Anna Timoshchuk | MSU Institute for Artificial Intelligence, Lomonosov Moscow State University
Abstract ID: 425
Event: BGRS-abstracts
Sections: [Sym 4] Section “Genome-wide association studies”

Glycosylation is co- and post-translational protein modification that impacts their physico-chemical properties, as well as biological functions. While the biochemical pathways of glycosylation are well studied, the genetic regulation of glycosylation remains incompletely understood. This complicates both the interpretation of the observed association between protein glycosylation levels and human diseases, as well as the development of glycan-based biomarkers and therapeutics. Here, we present results from the largest genome-wide association study of N-glycosylation of blood plasma proteome in 10,000 individuals. We identified 16 novel loci and prioritized 13 novel genes contributing to N-glycosylation. Among these were the glycosyltransferase ABO, as well as genes associated with lipid metabolism – GCKR, FADS2, TRIB1, and GRAMD1B. This is the first time protein N-glycosylation has been linked to genes involved in lipid metabolism and its regulation. We found causal relationships between high-mannose glycans, asthma, and lipoprotein metabolism disorders. By integrating glycomics, proteomics, transcriptomics and genomics, we provide a resource that facilitates deeper exploration of disease pathogenesis and supports drug discovery and development efforts.