TY - JOUR
T1 - Genetic regulation of post-translational modification of two distinct proteins
AU - Landini, Arianna
AU - Trbojević-Akmačić, Irena
AU - Navarro, Pau
AU - Tsepilov, Yakov A
AU - Sharapov, Sodbo Z
AU - Vučković, Frano
AU - Polašek, Ozren
AU - Hayward, Caroline
AU - Petrović, Tea
AU - Vilaj, Marija
AU - Aulchenko, Yurii S
AU - Lauc, Gordan
AU - Wilson, James F
AU - Klarić, Lucija
N1 - Funding Information:
We thank Dr Nicola Pirastu for sharing his knowledge and experience with Mendelian Randomisation and Jelena Šimunović for her technical assistance in the laboratory work. The CROATIA-Korcula study was funded by grants from the MRC (United Kingdom), European Commission Framework 6 project EUROSPAN (contract number LSHG-CT-2006-018947), Croatian Science Foundation (grant 8875) and the Republic of Croatia Ministry of Science, Education and Sports (216-1080315-0302). Genotyping was performed in the Genetics Core of the Clinical Research Facility, University of Edinburgh. We would like to acknowledge all the staff of several institutions in Croatia that supported the CROATIA-Korcula fieldwork, including, but not limited to, the University of Split and Zagreb Medical Schools, Institute for Anthropological Research in Zagreb, and the Croatian Institute for Public Health in Split. The Viking Health Study— Shetland (VIKING) was supported by the MRC Human Genetics Unit quinquennial programme grant ‘QTL in Health and Disease’. DNA extractions and genotyping were performed at the Edinburgh Clinical Research Facility, University of Edinburgh. We would like to acknowledge the invaluable contributions of the research nurses in Shetland, the administrative team in Edinburgh and the people of Shetland. Finally, we thank the UK Biobank Resource, approved under application 19655. We acknowledge support from the European Union’s Horizon 2020 research and innovation programme IMforFUTURE (A.L.: H2020-MSCA-ITN/721815); the RCUK Innovation Fellowship from the National Productivity Investment Fund (L.K.: MR/R026408/1); the Russian Science Foundation (RSF) (Y.S.A. and S.Z.S.: 19-15-00115); and the MRC Human Genetics Unit programme grant, ‘QTL in Health and Disease’ (J.F.W. and C.H.: MC_UU_00007/10).
Funding Information:
Ministry of Education, Singapore, under its Tier 2 Academic Research Fund (AcRF), Grant/Award Number: MOE2019‐T2‐1‐185; National Natural Science Foundation of China, Grant/Award Number: 71571176 Funding information
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/3/24
Y1 - 2022/3/24
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-022-29189-5
DO - 10.1038/s41467-022-29189-5
M3 - Article
C2 - 35332118
SN - 2041-1723
VL - 13
SP - 1586
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1586
ER -