Genetic regulation of post-translational modification of two distinct proteins

Arianna Landini, Irena Trbojević-Akmačić, Pau Navarro, Yakov A Tsepilov, Sodbo Z Sharapov, Frano Vučković, Ozren Polašek, Caroline Hayward, Tea Petrović, Marija Vilaj, Yurii S Aulchenko, Gordan Lauc, James F Wilson, Lucija Klarić

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation or influence on complex traits is not fully understood. Here, we compare the genetic regulation of the same PTM of two proteins - glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identify 10 significantly associated loci, 9 of which were not reported previously. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1), as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. Glycosylation of these proteins is thus genetically regulated by both shared and protein-specific mechanisms.

Original languageEnglish
Article number1586
Pages (from-to)1586
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 24 Mar 2022

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