Dataset Information

Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study.

ABSTRACT:

Objective

To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach.

Methods

We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was used to estimate the causal effects of LDL-C for IS and IS subtypes (based on 12,389 IS cases from METASTROKE) and for CHD (based on 60,801 cases from CARDIoGRAMplusC4D). We then assessed the effects of LDL-C on IS and CHD for heterogeneity.

Results

A 1 mmol/L higher genetically determined LDL-C was associated with a 50% higher risk of CHD (odds ratio [OR] 1.49, 95% confidence interval [CI] 1.32-1.68, p = 1.1 × 10^-8). By contrast, the causal effect of LDL-C was much weaker for IS (OR 1.12, 95% CI 0.96-1.30, p = 0.14; p for heterogeneity = 2.6 × 10^-3) and, in particular, for cardioembolic stroke (OR 1.06, 95% CI 0.84-1.33, p = 0.64; p for heterogeneity = 8.6 × 10^-3) when compared with that for CHD.

Conclusions

In contrast with the consistent effects of LDL-C-lowering therapies on IS and CHD, genetic variants that confer lifelong LDL-C differences show a weaker effect on IS than on CHD. The relevance of etiologically distinct IS subtypes may contribute to the differences observed.

SUBMITTER: Valdes-Marquez E

PROVIDER: S-EPMC6511103 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study.

Valdes-Marquez Elsa E Parish Sarah S Clarke Robert R Stari Traiani T Worrall Bradford B BB Hopewell Jemma C JC

Neurology 20190220 11

<h4>Objective</h4>To examine the causal relevance of lifelong differences in low-density lipoprotein cholesterol (LDL-C) for ischemic stroke (IS) relative to that for coronary heart disease (CHD) using a Mendelian randomization approach.<h4>Methods</h4>We undertook a 2-sample Mendelian randomization, based on summary data, to estimate the causal relevance of LDL-C for risk of IS and CHD. Information from 62 independent genetic variants with genome-wide significant effects on LDL-C levels was use ...[more]

PMID: 30787162

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Project description:Background: Atopic dermatitis (AD) is the most common chronic skin inflammatory disease. Prior observational studies have reported inconsistent results on the association of AD with ischemic stroke and coronary heart disease. In this study, we applied two-sample Mendelian randomization (MR) to evaluate the causal effect of AD on ischemic stroke and coronary heart disease. Methods: Twelve single-nucleotide polymorphisms robustly associated with AD (p < 5 × 10-8) were obtained from a genome-wide association study that included 10,788 cases and 30,047 controls by the EArly Genetics and Life course Epidemiology (EAGLE) Consortium (excluding the 23andMe study). The corresponding data for ischemic stroke (34,217 cases and 406,111 controls), large artery stroke (4,373 cases and 406,111 controls), cardioembolic stroke (7,193 cases and 406,111 controls), small vessel stroke (5,386 cases and 192,662 controls), coronary heart disease (122,733 cases and 424,528 controls), and myocardial infarction (43,676 cases and 128,199 controls) were obtained from the MR-Base platform. In the primary MR analyses, we applied the inverse variance weighted method to evaluate the associations. We performed a sensitivity analysis using weighted median, MR-Egger, weighted mode, simple mode, Mendelian Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out methods. Results: In the primary MR analyses, we found no causal association of genetically predicted AD with ischemic stroke [odds ratio (OR) = 1.00, 95% confidence interval (CI): 0.95-1.06], large artery stroke (OR = 1.02, 95% CI: 0.88-1.17), cardioembolic stroke (OR = 1.06, 95% CI: 0.94-1.18), small vessel stroke (OR = 1.05, 95% CI: 0.94-1.17), coronary heart disease (OR = 1.00, 95% CI: 0.94-1.05), and myocardial infarction (OR = 1.03, 95% CI: 0.98-1.09). The results from the primary MR analyses were supported in sensitivity analyses using the weighted median, weighted mode, simple mode, and MR-Egger methods and multivariable MR analyses adjusting for asthma and several traditional risk factors for ischemic stroke and coronary heart disease. MR-Egger intercepts provided no evidence of directional pleiotropy. The MR-PRESSO and leave-one-out analyses did not indicate any outlier instruments. Conclusion: Our MR study does not support a causal association of genetically predicted AD with ischemic stroke, large artery stroke, cardioembolic stroke, small vessel stroke, coronary heart disease, and myocardial infarction.

Dataset Information

Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study.

Objective

Methods

Results

Conclusions

Publications

Relative effects of LDL-C on ischemic stroke and coronary disease: A Mendelian randomization study.

Similar Datasets

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