Genetically predicted lipid traits mediate the association between folic acid and atherosclerosis.
Atherosclerosis
Folic acid
High-density lipoprotein cholesterol
Low-density lipoprotein cholesterol
Mendelian randomization
Triglycerides
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
17 Aug 2024
17 Aug 2024
Historique:
received:
30
10
2023
accepted:
08
08
2024
medline:
18
8
2024
pubmed:
18
8
2024
entrez:
17
8
2024
Statut:
epublish
Résumé
Atherosclerosis (AS) is one of the most common causes of death from cardiovascular disease, and low folic acid (FA) levels have been reported to be strongly associated with an increased risk of AS. We aimed to obtain causal estimates of the association between FA and AS and to quantify the mediating role of known modifiable risk factors. Based on the largest genome-wide association study (GWAS) from the IEU Open GWAS Project for all human studies, we conducted a two-sample Mendelian randomization (MR) study of genetically predicted FA and AS. A two-step MR design was then used to assess the causal mediating effect of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) on the relationship between FA and AS. This MR analysis showed that genetically determined FA levels [IVW: Odds Ratio (OR) = 0.623, 95% CI 0.421-0.924, P = 0.018] were associated with a reduced risk of AS. Inverse variance weighted (IVW) MR analysis also showed that genetically predicted FA was positively correlated with HDL-C levels (OR = 1.358, 95% CI 1.029-1.792, P = 0.031) and negatively correlated with LDL-C (OR = 0.956, 95% CI 0.920-0.994, P = 0.023) and TG levels (OR = 0.929, 95% CI 0.886-0.974, P = 0.003). LDL-C, HDL-C, and TG mediate 3.00%, 6.80%, and 4.40%, respectively, of the total impact of FA on AS. The combined effect of these three factors accounts for 13.04% of the total effect. Sensitivity analysis verifies the stability and reliability of the results. These results support a potential causal protective effect of FA on AS, with considerable mediation through many modifiable risk factors. Thus, interventions on levels of LDL-C, HDL-C, and TG have the potential to substantially reduce the burden of AS caused by low FA.
Identifiants
pubmed: 39154068
doi: 10.1038/s41598-024-69728-2
pii: 10.1038/s41598-024-69728-2
doi:
Substances chimiques
Folic Acid
935E97BOY8
Triglycerides
0
Cholesterol, LDL
0
Cholesterol, HDL
0
Lipids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
19052Subventions
Organisme : Scientific and Technological Talents Support Program of Shaanxi Provincial People's Hospital
ID : 2022JY-69
Organisme : Science and Technology Development Incubation Fund Project of Shaanxi Provincial People's Hospital in 2022
ID : 2022YJY-53
Organisme : The Science and Technology Project of Shaanxi Province
ID : 2022SF-152
Informations de copyright
© 2024. The Author(s).
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