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Sharapov, S.Z.* ; Shadrina, A.S.* ; Tsepilov, Y.A.* ; Elgaeva, E.E.* ; Tiys, E.S.* ; Feoktistova, S.G.* ; Zaytseva, O.O.* ; Vučković, F.* ; Cuadrat, R.* ; Jäger, S.* ; Wittenbecher, C.* ; Karssen, L.C.* ; Timofeeva, M.* ; Tillin, T.* ; Trbojević-Akmačić, I.* ; Štambuk, T.* ; Rudman, N.* ; Krištić, J.* ; Šimunović, J.* ; Momčilović, A.* ; Vilaj, M.* ; Jurić, J.* ; Slana, A.* ; Gudelj, I.* ; Klarić, T.* ; Puljak, L.* ; Skelin, A.* ; Kadić, A.J.* ; Van Zundert, J.* ; Chaturvedi, N.* ; Campbell, H.* ; Dunlop, M.* ; Farrington, S.M.* ; Doherty, M.* ; Dagostino, C.* ; Gieger, C. ; Allegri, M.* ; Williams, F.* ; Schulze, M.B.* ; Lauc, G.* ; Aulchenko, Y.S.*

Replication of fifteen loci involved in human plasma protein N-glycosylation in 4,802 samples from four cohorts.

Glycobiology 31, 82-88 (2021)
Verlagsversion Postprint Forschungsdaten DOI
Open Access Green
Human protein glycosylation is a complex process, and its in vivo regulation is poorly understood. Changes in glycosylation patterns are associated with many human diseases and conditions. Understanding the biological determinants of protein glycome provides a basis for future diagnostic and therapeutic applications. Genome-wide association studies (GWAS) allow to study biology via a hypothesis-free search of loci and genetic variants associated with a trait of interest. Sixteen loci were identified by three previous GWAS of human plasma proteome N-glycosylation. However, the possibility that some of these loci are false positives needs to be eliminated by replication studies, which have been limited so far. Here, we use the largest set of samples so far (4,802 individuals) to replicate the previously identified loci. For all but one locus, the expected replication power exceeded 95%. Of the sixteen loci reported previously, fifteen were replicated in our study. For the remaining locus (near the KREMEN1 gene) the replication power was low, and hence replication results were inconclusive. The very high replication rate highlights the general robustness of the GWAS findings as well as the high standards adopted by the community that studies genetic regulation of protein glycosylation. The fifteen replicated loci present a good target for further functional studies. Among these, eight genes encode glycosyltransferases: MGAT5, B3GAT1, FUT8, FUT6, ST6GAL1, B4GALT1, ST3GAL4, and MGAT3. The remaining seven loci offer starting points for further functional follow-up investigation into molecules and mechanisms that regulate human protein N-glycosylation in vivo.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genetic Association Study ; Glycosylation ; Locus ; Replication ; Total Plasma N-glycome; Immunoglobulin-g; Golgi Ph
ISSN (print) / ISBN 0959-6658
e-ISSN 1460-2423
Zeitschrift Glycobiology
Quellenangaben Band: 31, Heft: 2, Seiten: 82-88 Artikelnummer: , Supplement: ,
Verlag Oxford Univ Press Inc
Verlagsort Oxford, UK
Begutachtungsstatus Peer reviewed
Förderungen Diabetes UK
Wellcome Trust
European Community's Seventh Framework Programme
Cancer Research UK
Croatian National Centre of Research Excellence in Personalized Healthcare grant
European Structural and Investment Funds IRI grant
PolyOmica, the Netherlands
Federal Agency of Scientific Organizations via the Institute of Cytology and Genetics
Russian Ministry of Science and Education under the 5-100 Excellence Programme
British Heart Foundation
National Institute for Health Research University College London Hospitals Biomedical Research Centre
MRC Human Genetics Unit Centre grant
Edinburgh CRUK Cancer Research Centre
Centre Grant from CORE as part of the Digestive Cancer Campaign
Medical Research Council
Scottish Government Chief Scientist Office
State of Brandenburg
German Ministry of Education and Research (BMBF)
European Community
German Cancer Aid
European Union
Federal Ministry of Science, Germany
Russian Science Foundation