Evaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on Aging
Abstract High intraocular pressure (IOP) is an important risk factor for glaucoma, which is influenced by genetic and environmental factors. However, the etiology of high IOP remains uncertain. Metabolites are compounds involved in metabolism which provide a link between the internal (genetic) and e...
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2025-01-01
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| Online Access: | https://doi.org/10.1186/s12863-025-01301-w |
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| author | Rebecca Lelievre Mohan Rakesh Pirro G. Hysi Julian Little Ellen E. Freeman Marie-Hélène Roy-Gagnon |
| author_facet | Rebecca Lelievre Mohan Rakesh Pirro G. Hysi Julian Little Ellen E. Freeman Marie-Hélène Roy-Gagnon |
| author_sort | Rebecca Lelievre |
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| description | Abstract High intraocular pressure (IOP) is an important risk factor for glaucoma, which is influenced by genetic and environmental factors. However, the etiology of high IOP remains uncertain. Metabolites are compounds involved in metabolism which provide a link between the internal (genetic) and external environments. O-methylascorbate has been reported to be associated with IOP. In addition, researchers have identified several genetic variants which are associated with metabolite concentrations, including O-methylascorbate and another vitamin C related metabolite, ascorbic acid 2-sulfate. We aimed to understand how O-methylascorbate and ascorbic acid 2-sulfate, or genetic variants associated with these metabolites, modify the associations between dietary environmental variables and IOP. We used data from 8060 participants of the Canadian Longitudinal Study on Aging. Using linear models adjusted for relevant covariates, we tested for interactions between six genetic variants previously found to be associated with O-methylascorbate and ascorbic acid 2-sulfate and four environmental variables related to diet (alcohol consumption frequency, smoking status, fruit consumption, and vegetable consumption). We also tested for interactions between serum concentrations of O-methylascorbate and ascorbic acid 2-sulfate and these environmental factors. We used a False Discovery Rate approach to correct for the 32 interaction tests performed. One interaction was suggestively significant after multiple testing correction (adjusted P-value < 0.1): rs8050812 and alcohol consumption frequency. Understanding how genetic variants and metabolites interact with the environment could shed light on biological pathways controlling IOP and lead to improved prevention and treatment of glaucoma. |
| format | Article |
| id | doaj-art-559741826f114bc9ad1aeb7f7b84c3c2 |
| institution | Kabale University |
| issn | 2730-6844 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | BMC Genomic Data |
| spelling | doaj-art-559741826f114bc9ad1aeb7f7b84c3c22025-02-02T12:44:36ZengBMCBMC Genomic Data2730-68442025-01-012611910.1186/s12863-025-01301-wEvaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on AgingRebecca Lelievre0Mohan Rakesh1Pirro G. Hysi2Julian Little3Ellen E. Freeman4Marie-Hélène Roy-Gagnon5School of Epidemiology and Public Health, University of OttawaSchool of Epidemiology and Public Health, University of OttawaSection of Ophthalmology, School of Life Course Sciences, King’s College LondonSchool of Epidemiology and Public Health, University of OttawaSchool of Epidemiology and Public Health, University of OttawaSchool of Epidemiology and Public Health, University of OttawaAbstract High intraocular pressure (IOP) is an important risk factor for glaucoma, which is influenced by genetic and environmental factors. However, the etiology of high IOP remains uncertain. Metabolites are compounds involved in metabolism which provide a link between the internal (genetic) and external environments. O-methylascorbate has been reported to be associated with IOP. In addition, researchers have identified several genetic variants which are associated with metabolite concentrations, including O-methylascorbate and another vitamin C related metabolite, ascorbic acid 2-sulfate. We aimed to understand how O-methylascorbate and ascorbic acid 2-sulfate, or genetic variants associated with these metabolites, modify the associations between dietary environmental variables and IOP. We used data from 8060 participants of the Canadian Longitudinal Study on Aging. Using linear models adjusted for relevant covariates, we tested for interactions between six genetic variants previously found to be associated with O-methylascorbate and ascorbic acid 2-sulfate and four environmental variables related to diet (alcohol consumption frequency, smoking status, fruit consumption, and vegetable consumption). We also tested for interactions between serum concentrations of O-methylascorbate and ascorbic acid 2-sulfate and these environmental factors. We used a False Discovery Rate approach to correct for the 32 interaction tests performed. One interaction was suggestively significant after multiple testing correction (adjusted P-value < 0.1): rs8050812 and alcohol consumption frequency. Understanding how genetic variants and metabolites interact with the environment could shed light on biological pathways controlling IOP and lead to improved prevention and treatment of glaucoma.https://doi.org/10.1186/s12863-025-01301-wCLSAGene-environmentIntraocular pressureMetabolites |
| spellingShingle | Rebecca Lelievre Mohan Rakesh Pirro G. Hysi Julian Little Ellen E. Freeman Marie-Hélène Roy-Gagnon Evaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on Aging BMC Genomic Data CLSA Gene-environment Intraocular pressure Metabolites |
| title | Evaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on Aging |
| title_full | Evaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on Aging |
| title_fullStr | Evaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on Aging |
| title_full_unstemmed | Evaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on Aging |
| title_short | Evaluating vitamin C-related gene-environment and metabolite-environment interaction effects on intraocular pressure in the Canadian Longitudinal Study on Aging |
| title_sort | evaluating vitamin c related gene environment and metabolite environment interaction effects on intraocular pressure in the canadian longitudinal study on aging |
| topic | CLSA Gene-environment Intraocular pressure Metabolites |
| url | https://doi.org/10.1186/s12863-025-01301-w |
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