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Association of high sensitive C-reactive protein with coronary heart disease: a Mendelian randomization study.

ABSTRACT: OBJECTIVES:Whether high sensitivity C-reactive protein (hs-CRP) has a causal effect on coronary heart disease (CHD) is unclear. This study investigated the causal effect of hs-CRP on CHD risk using Mendelian Randomization (MR) analysis. METHODS:A total of 3802 subjects were recruited in the follow-up study. Linear regression model was used to evaluate the relationship between CRP polymorphisms and hs-CRP. Survival receiver operator characteristic curve method was used to explore the cut-off of hs-CRP on CHD incidence. Cox regression model was applied to detect the association of hs-CRP with CHD by calculating the hazard ratio (HR) and 95% confidence interval (CI). Rs1205 and rs876537 in CRP were selected as instrumental variables in MR analysis. RESULTS:During a median follow-up time of 5.01?years, 98 CHD incidence was identified (47.03/104 person-years). Hs-CRP was significantly increased among rs1205 and rs876537 genotypes with r values of 0.064 and 0.066, respectively. Hs-CRP 1.08?mg/L was identified as the cut-off value with a maximum value of sensitivity and specificity on prediction of CHD. Participants with ?1.08?mg/L of hs-CRP has a higher risk of CHD incidence than that of participants with

SUBMITTER: Zhuang Q

PROVIDER: S-EPMC6836320 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Association of high sensitive C-reactive protein with coronary heart disease: a Mendelian randomization study.

Zhuang Qian Q Shen Chong C Chen Yanchun Y Zhao Xianghai X Wei Pengfei P Sun Junxiang J Ji Yanni Y Chen Xiaotian X Yang Song S

BMC medical genetics 20191106 1

<h4>Objectives</h4>Whether high sensitivity C-reactive protein (hs-CRP) has a causal effect on coronary heart disease (CHD) is unclear. This study investigated the causal effect of hs-CRP on CHD risk using Mendelian Randomization (MR) analysis.<h4>Methods</h4>A total of 3802 subjects were recruited in the follow-up study. Linear regression model was used to evaluate the relationship between CRP polymorphisms and hs-CRP. Survival receiver operator characteristic curve method was used to explore t ...[more]

PMID: 31694563

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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.

Project description:BackgroundMajor depressive disorder (MDD) is a highly heterogeneous mental illness and a major public health problem worldwide. A large number of observational studies have demonstrated a clear association between MDD and coronary heart disease (CHD), and some studies have even suggested that the relationship is bidirectional. However, it was unknown whether any causal relationship existed between them and whether causality was bidirectional in such an instance. Thus, we aimed to determine whether there is a bidirectional causal relationship between major depressive disorders and coronary heart disease.MethodsOur two-sample Bidirectional Mendelian Randomization Study consisted of two parts: forward MR analysis regarded MDD as exposure and CHD as the outcome, and reverse MR analysis considered CHD as exposure and MDD as the outcome. Summary data on MDD and CHD were obtained from the IEU Open GWAS database. After screening criteria(P < [Formula: see text]), 47 MDD-associated SNPs and 39 CHD-associated SNPs were identified. The inverse-variance weighted (IVW) method, ME-Egger regression, and weighted median method were used to estimate causality. In addition, sensitivity methods, including the heterogeneity test, horizontal pleiotropy test, and leave-one-out method, were applied to ensure the robustness of causal estimation.ResultsBased on the MR-Egger regression intercept test results, there did not appear to be any horizontal pleiotropy in this study (MDD: intercept = -0.0000376, P = 0.9996; CHD: intercept = -0.0002698, P = 0.920). Accordingly, IVW results suggested consistent estimates of causal effect values. The results showed that people with MDD increased the risk of CHD by 14.7% compared with those without MDD (OR = 1.147, 95%CI: 1.045-1.249, P = 0.009). But there was no direct evidence that CHD would increase the risk of MDD(OR = 1.008, 95%CI: 0.985-1.031, P = 0.490). The heterogeneity test and funnel plot showed no heterogeneity in 47 SNPs of MDD (Q = 42.28, [Formula: see text]=0, P = 0.629), but there was heterogeneity in 39 SNPs of CHD (Q = 62.48, [Formula: see text]=39.18%, P = 0.007). The leave-one-out method failed to identify instances where a single SNP was either biased toward or dependent on the causation.ConclusionOur study supports a one-way causal relationship between MDD and CHD, but there is no bidirectional causal relationship. MDD increases the risk of CHD, but there is no evidence that CHD increases the risk of MDD. Therefore, the influence of psychological factors should also be considered in the prevention and treatment of CHD. For MDD patients, it is necessary to prevent cardiovascular diseases.

Project description:BackgroundFibrinogen is an essential hemostatic factor and cardiovascular disease risk factor. Early attempts at evaluating the causal effect of fibrinogen on coronary heart disease (CHD) and myocardial infraction (MI) using Mendelian randomization (MR) used single variant approaches, and did not take advantage of recent genome-wide association studies (GWAS) or multi-variant, pleiotropy robust MR methodologies.Methods and findingsWe evaluated evidence for a causal effect of fibrinogen on both CHD and MI using MR. We used both an allele score approach and pleiotropy robust MR models. The allele score was composed of 38 fibrinogen-associated variants from recent GWAS. Initial analyses using the allele score used a meta-analysis of 11 European-ancestry prospective cohorts, free of CHD and MI at baseline, to examine incidence CHD and MI. We also applied 2 sample MR methods with data from a prevalent CHD and MI GWAS. Results are given in terms of the hazard ratio (HR) or odds ratio (OR), depending on the study design, and associated 95% confidence interval (CI). In single variant analyses no causal effect of fibrinogen on CHD or MI was observed. In multi-variant analyses using incidence CHD cases and the allele score approach, the estimated causal effect (HR) of a 1 g/L higher fibrinogen concentration was 1.62 (CI = 1.12, 2.36) when using incident cases and the allele score approach. In 2 sample MR analyses that accounted for pleiotropy, the causal estimate (OR) was reduced to 1.18 (CI = 0.98, 1.42) and 1.09 (CI = 0.89, 1.33) in the 2 most precise (smallest CI) models, out of 4 models evaluated. In the 2 sample MR analyses for MI, there was only very weak evidence of a causal effect in only 1 out of 4 models.ConclusionsA small causal effect of fibrinogen on CHD is observed using multi-variant MR approaches which account for pleiotropy, but not single variant MR approaches. Taken together, results indicate that even with large sample sizes and multi-variant approaches MR analyses still cannot exclude the null when estimating the causal effect of fibrinogen on CHD, but that any potential causal effect is likely to be much smaller than observed in epidemiological studies.

Dataset Information

Association of high sensitive C-reactive protein with coronary heart disease: a Mendelian randomization study.

Publications

Association of high sensitive C-reactive protein with coronary heart disease: a Mendelian randomization study.

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