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Effect modification by sex of genetic associations of vitamin C related metabolites in the Canadian Longitudinal study on aging
- Source :
- Frontiers in Genetics, Vol 15 (2024)
- Publication Year :
- 2024
- Publisher :
- Frontiers Media S.A., 2024.
-
Abstract
- Introduction: Vitamin C is an essential nutrient. Sex differences in serum vitamin C concentrations have been observed but are not fully known. Investigation of levels of metabolites may help shed light on how dietary and other environmental exposures interact with molecular processes. O-methylascorbate and ascorbic acid 2-sulfate are two metabolites in the vitamin C metabolic pathway. Past research has found genetic factors that influence the levels of these two metabolites. Therefore, we investigated possible effect modification by sex of genetic variant-metabolite associations and characterized the biological function of these interactions.Methods: We included individuals of European descent from the Canadian Longitudinal Study on Aging with available genetic and metabolic data (n = 9004). We used linear mixed models to tests for genome-wide associations with O-methylascorbate and ascorbic acid 2-sulfate, with and without a sex interaction. We also investigated the biological function of the important genetic variant-sex interactions found for each metabolite.Results: Two genome-wide statistically significant (p value < 5 × 10−8) interaction effects and several suggestive (p value < 10–5) interaction effects were found. These suggestive interaction effects were mapped to several genes including HSD11B2, associated with sex hormones, and AGRP, associated with hunger drive. The genes mapped to O-methylascorbate were differently expressed in the testis tissues, and the genes mapped to ascorbic acid 2-sulfate were differently expressed in stomach tissues.Discussion: By understanding the genetic factors that impact metabolites associated with vitamin C, we can better understand its function in disease risk and the mechanisms behind sex differences in vitamin C concentrations.
- Subjects :
- vitamin C
metabolites
GWAS
gene-environment interaction
CLSA
Genetics
QH426-470
Subjects
Details
- Language :
- English
- ISSN :
- 16648021
- Volume :
- 15
- Database :
- Directory of Open Access Journals
- Journal :
- Frontiers in Genetics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.bcb1fcbda2dc4c87bf5d6fe2281c5529
- Document Type :
- article
- Full Text :
- https://doi.org/10.3389/fgene.2024.1411931