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Impact of gallstone disease on the risk of stroke and coronary artery disease: evidence from prospective observational studies and genetic analyses.
Zhang, Li; Zhang, Wenqiang; He, Lin; Cui, Huijie; Wang, Yutong; Wu, Xueyao; Zhao, Xunying; Yan, Peijing; Yang, Chao; Xiao, Changfeng; Tang, Mingshuang; Chen, Lin; Xiao, Chenghan; Zou, Yanqiu; Liu, Yunjie; Yang, Yanfang; Zhang, Ling; Yao, Yuqin; Li, Jiayuan; Liu, Zhenmi; Yang, Chunxia; Jiang, Xia; Zhang, Ben.
Affiliation
  • Zhang L; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Zhang W; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • He L; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Cui H; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Wang Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Wu X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Zhao X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Yan P; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Yang C; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Xiao C; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Tang M; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Chen L; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Xiao C; Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • Zou Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Liu Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Yang Y; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Zhang L; Department of Iatrical Polymer Material and Artificial Apparatus, School of Polymer Science and Engineering, Sichuan University, Chengdu, China.
  • Yao Y; Department of Occupational and Environmental Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • Li J; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Liu Z; Department of Maternal, Child and Adolescent Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
  • Yang C; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China.
  • Jiang X; Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, and West China-PUMC C. C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, No. 16, Section 3, South Renmin Road, Wuhou District, Chengdu, 610041, China. xi
  • Zhang B; Department of Nutrition and Food Hygiene, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China. xiajiang@scu.edu.cn.
BMC Med ; 21(1): 353, 2023 09 13.
Article in 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Stroke / Myocardial Infarction Type of study: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: BMC Med Journal subject: MEDICINA Year: 2023 Type: Article Affiliation country: China
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Coronary Artery Disease / Stroke / Myocardial Infarction Type of study: Clinical_trials / Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: BMC Med Journal subject: MEDICINA Year: 2023 Type: Article Affiliation country: China