Mapping of the gene network that regulates glycan clock of ageing Article Swipe
Azra Frkatović-Hodžić
,
Anika Mijakovac
,
Karlo Miškec
,
Arina Nostaeva
,
Sodbo Sharapov
,
Arianna Landini
,
Toomas Haller
,
Erik B. van den Akker
,
Sapna Sharma
,
Rafael R. C. Cuadrat
,
Massimo Mangino
,
Yong Li
,
Toma Keser
,
Najda Rudman
,
Tamara Štambuk
,
Maja Pučić‐Baković
,
Irena Trbojević‐Akmačić
,
Ivan Gudelj
,
Jerko Štambuk
,
Tea Pribić
,
Barbara Radovani
,
Petra Tominac
,
Krista Fischer
,
Marian Beekman
,
Manfred Wuhrer
,
Christian Gieger
,
Matthias B. Schulze
,
Clemens Wittenbecher
,
Ozren Polašek
,
Caroline Hayward
,
James F. Wilson
,
Tim D. Spector
,
Anna Köttgen
,
Frano Vučković
,
Yurii S. Aulchenko
,
Aleksandar Vojta
,
Jasminka Krištić
,
Lucija Klarić
,
Vlatka Zoldoš
,
Gordan Lauc
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.18632/aging.205106
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.18632/aging.205106
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.
Related Topics
Concepts
Glycome
Gene
Glycosylation
Biology
Glycan
Genome-wide association study
Genetics
Glycoprotein
Single-nucleotide polymorphism
Genotype
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.18632/aging.205106
- https://www.aging-us.com/article/205106/pdf
- OA Status
- hybrid
- Cited By
- 6
- References
- 89
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4390226902
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4390226902Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.18632/aging.205106Digital Object Identifier
- Title
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Mapping of the gene network that regulates glycan clock of ageingWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-12-26Full publication date if available
- Authors
-
Azra Frkatović-Hodžić, Anika Mijakovac, Karlo Miškec, Arina Nostaeva, Sodbo Sharapov, Arianna Landini, Toomas Haller, Erik B. van den Akker, Sapna Sharma, Rafael R. C. Cuadrat, Massimo Mangino, Yong Li, Toma Keser, Najda Rudman, Tamara Štambuk, Maja Pučić‐Baković, Irena Trbojević‐Akmačić, Ivan Gudelj, Jerko Štambuk, Tea Pribić, Barbara Radovani, Petra Tominac, Krista Fischer, Marian Beekman, Manfred Wuhrer, Christian Gieger, Matthias B. Schulze, Clemens Wittenbecher, Ozren Polašek, Caroline Hayward, James F. Wilson, Tim D. Spector, Anna Köttgen, Frano Vučković, Yurii S. Aulchenko, Aleksandar Vojta, Jasminka Krištić, Lucija Klarić, Vlatka Zoldoš, Gordan LaucList of authors in order
- Landing page
-
https://doi.org/10.18632/aging.205106Publisher landing page
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https://www.aging-us.com/article/205106/pdfDirect link to full text PDF
- Open access
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YesWhether a free full text is available
- OA status
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hybridOpen access status per OpenAlex
- OA URL
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https://www.aging-us.com/article/205106/pdfDirect OA link when available
- Concepts
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Glycome, Gene, Glycosylation, Biology, Glycan, Genome-wide association study, Genetics, Glycoprotein, Single-nucleotide polymorphism, GenotypeTop concepts (fields/topics) attached by OpenAlex
- Cited by
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6Total citation count in OpenAlex
- Citations by year (recent)
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2025: 3, 2024: 2, 2023: 1Per-year citation counts (last 5 years)
- References (count)
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89Number of works referenced by this work
- Related works (count)
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10Other works algorithmically related by OpenAlex
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