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A Mendelian randomization study of the effect of calcium on coronary artery disease, myocardial infarction and their risk factors.

ABSTRACT: Meta-analyses of randomized controlled trials (RCTs) suggest calcium could have adverse effects on cardiovascular disease, although these findings are controversial. To clarify, we assessed whether people with genetically higher calcium had a higher risk of coronary artery disease (CAD), myocardial infarction (MI) and their risk factors. We used a two-sample Mendelian randomization study. We identified genetic variants (single nucleotide polymorphisms (SNPs)) that independently contributed to serum calcium at genome-wide significance which we applied to large extensively genotyped studies of CAD, MI, diabetes, lipids, glycaemic traits and adiposity to obtain unconfounded estimates, with body mass index (BMI) as a control outcome. Based on 4 SNPs each 1?mg/dl increase in calcium was positively associated with CAD (odds ratio (OR) 1.49, 95% confidence interval (CI) 1.02-2.17), MI (OR 1.58, 95% CI 1.06-2.35), LDL-cholesterol (0.21 standard deviations, 95% CI 0.01-0.4), total cholesterol (0.21 standard deviations, 95% CI 0.03-0.38) and possibly triglycerides (0.19 standard deviations, 95% CI -0.1-0.48), but was unlikely related to BMI although the estimate lacked precision. Sensitivity analysis using 13 SNPs showed a higher risk for CAD (OR 1.87, 95% CI 1.14-3.08). Our findings, largely consistent with the experimental evidence, suggest higher serum calcium may increase the risk of CAD.

SUBMITTER: Xu L

PROVIDER: S-EPMC5307362 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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A Mendelian randomization study of the effect of calcium on coronary artery disease, myocardial infarction and their risk factors.

Xu Lin L Lin Shi Lin SL Schooling C Mary CM

Scientific reports 20170214

Meta-analyses of randomized controlled trials (RCTs) suggest calcium could have adverse effects on cardiovascular disease, although these findings are controversial. To clarify, we assessed whether people with genetically higher calcium had a higher risk of coronary artery disease (CAD), myocardial infarction (MI) and their risk factors. We used a two-sample Mendelian randomization study. We identified genetic variants (single nucleotide polymorphisms (SNPs)) that independently contributed to se ...[more]

PMID: 28195141

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Project description:Background: Previous studies have indicated that the gut microbiota (GM) is associated with coronary artery disease (CAD), but the causality of these associations remains unestablished due to confounding factors and reverse causality. We conducted Mendelian randomization study (MR) to determine the causal effect of the specific bacterial taxa on CAD/myocardial infarction (MI) and identify the mediating factors involved. Methods: Two-sample MR, multivariable MR (MVMR) and mediation analysis were performed. Inverse-variance weighting (IVW) was the main method used to analyze causality, and sensitivity analysis was used to verify the reliability of the study. Causal estimates from CARDIoGRAMplusC4D and FinnGen databases were combined using the meta-analysis method, and repeated validation was conducted based on the UK Biobank (UKB) database. Confounders that may affect the causal estimates were corrected by MVMP and the potential mediation effects were investigated by using mediation analysis. Results: The study suggested that increased abundance of the RuminococcusUCG010 genus leads to a lower risk of CAD (OR, 0.88; 95% CI, 0.78, 1.00; p = 2.88 × 10-2) and MI (OR, 0.88; 95% CI, 0.79, 0.97; p = 1.08 × 10-2), with consistent results in both meta-analysis (CAD: OR, 0.86; 95% CI, 0.78, 0.96; p = 4.71 × 10-3; MI: OR, 0.82; 95% CI, 0.73, 0.92; p = 8.25 × 10-4) and repeated analysis of the UKB dataset (CAD: OR, 0.99; 95% CI, 0.99, 1.00, p = 2.53 × 10-4; MI: OR, 0.99; 95% CI, 0.99, 1.00, p = 1.85 × 10-11). Based on multiple databases, T2DM was proved as a mediating factor in the causal effect of RuminococcusUCG010 and CAD/MI, with an average mediation effect proportion of 20% on CAD and 17% on MI, respectively. Conclusion: This MR study provided suggestive genetic evidence that the higher the RuminococcusUCG010 abundance is, the lower the risk of CAD and MI, with T2DM playing a mediating effect. This genus may become a novel target in strategies for treating and preventing CAD and MI.

Dataset Information

A Mendelian randomization study of the effect of calcium on coronary artery disease, myocardial infarction and their risk factors.

Publications

A Mendelian randomization study of the effect of calcium on coronary artery disease, myocardial infarction and their risk factors.

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