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Frkatović-Hodžić, A.* ; Mijakovac, A.* ; Miškec, K.* ; Nostaeva, A.* ; Sharapov, S.Z.* ; Landini, A.* ; Haller, T.* ; Akker, E.V.D.* ; Sharma, S. ; Cuadrat, R.R.C. ; Mangino, M.* ; Li, Y.* ; Keser, T.* ; Rudman, N.* ; Štambuk, T.* ; Pučić-Baković, M.* ; Trbojević-Akmačić, I.* ; Gudelj, I.* ; Štambuk, J.* ; Pribić, T.* ; Radovani, B.* ; Tominac, P.* ; Fischer, K.* ; Beekman, M.* ; Wuhrer, M.* ; Gieger, C. ; Schulze, M.B.* ; Wittenbecher, C.* ; Polasek, O.* ; Hayward, C.* ; Wilson, J.F.* ; Spector, T.D.* ; Köttgen, A.* ; Vučković, F.* ; Aulchenko, Y.S.* ; Vojta, A.* ; Krištić, J.* ; Klarić, L.* ; Zoldoš, V.* ; Lauc, G.*

Mapping of the gene network that regulates glycan clock of ageing.

Aging 15, 14509-14552 (2023)
DOI PMC
Creative Commons Lizenzvertrag
Glycans are an essential structural component of immunoglobulin G (IgG) that modulate its structure and function. However, regulatory mechanisms behind this complex posttranslational modification are not well known. Previous genome-wide association studies (GWAS) identified 29 genomic regions involved in regulation of IgG glycosylation, but only a few were functionally validated. One of the key functional features of IgG glycosylation is the addition of galactose (galactosylation), a trait which was shown to be associated with ageing. We performed GWAS of IgG galactosylation (N=13,705) and identified 16 significantly associated loci, indicating that IgG galactosylation is regulated by a complex network of genes that extends beyond the galactosyltransferase enzyme that adds galactose to IgG glycans. Gene prioritization identified 37 candidate genes. Using a recently developed CRISPR/dCas9 system we manipulated gene expression of candidate genes in the in vitro IgG expression system. Upregulation of three genes, EEF1A1, MANBA and TNFRSF13B, changed the IgG glycome composition, which confirmed that these three genes are involved in IgG galactosylation in this in vitro expression system.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Crispr/dcas9 ; Genome-wide Association Study ; Glycan Clock ; Glycosylation ; Immunoglobulin G
ISSN (print) / ISBN 1945-4589
e-ISSN 1945-4589
Journal Aging
Quellenangaben Volume: 15, Issue: 24, Pages: 14509-14552 Article Number: , Supplement: ,
Publisher Impact Journals LLC
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)