Impact of gallstone disease on the risk of stroke and coronary artery disease: evidence from prospective observational studies and genetic analyses.
BMC Med
; 21(1): 353, 2023 09 13.
Article
em En
| MEDLINE
| ID: mdl-37705021
ABSTRACT
BACKGROUND:
Despite epidemiological evidence associating gallstone disease (GSD) with cardiovascular disease (CVD), a dilemma remains on the role of cholecystectomy in modifying the risk of CVD. We aimed to characterize the phenotypic and genetic relationships between GSD and two CVD events - stroke and coronary artery disease (CAD).METHODS:
We first performed a meta-analysis of cohort studies to quantify an overall phenotypic association between GSD and CVD. We then investigated the genetic relationship leveraging the largest genome-wide genetic summary statistics. We finally examined the phenotypic association using the comprehensive data from UK Biobank (UKB).RESULTS:
An overall significant effect of GSD on CVD was found in meta-analysis (relative risk [RR] = 1.26, 95% confidence interval [CI] = 1.19-1.34). Genetically, a positive shared genetic basis was observed for GSD with stroke ([Formula see text]=0.16, P = 6.00 × 10-4) and CAD ([Formula see text]=0.27, P = 2.27 × 10-15), corroborated by local signals. The shared genetic architecture was largely explained by the multiple pleiotropic loci identified in cross-phenotype association study and the shared gene-tissue pairs detected by transcriptome-wide association study, but not a causal relationship (GSD to CVD) examined through Mendelian randomization (MR) (GSD-stroke odds ratio [OR] = 1.00, 95%CI = 0.97-1.03; GSD-CAD OR = 1.01, 95%CI = 0.98-1.04). After a careful adjustment of confounders or considering lag time using UKB data, no significant phenotypic effect of GSD on CVD was detected (GSD-stroke hazard ratio [HR] = 0.95, 95%CI = 0.83-1.09; GSD-CAD HR = 0.98, 95%CI = 0.91-1.06), further supporting MR findings.CONCLUSIONS:
Our work demonstrates a phenotypic and genetic relationship between GSD and CVD, highlighting a shared biological mechanism rather than a direct causal effect. These findings may provide insight into clinical and public health applications.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
/
Acidente Vascular Cerebral
/
Infarto do Miocárdio
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article