Association of smoking with coronary artery disease and myocardial infarction: A Mendelian randomization study

2020 ◽  
pp. 204748732090774 ◽  
Author(s):  
Yunlong Lu ◽  
Zhen Wang ◽  
Liangrong Zheng
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Artery Disease

scholarly journals Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study

2021 ◽  
Author(s):  
Martin Bahls ◽  
Michael F. Leitzmann ◽  
André Karch ◽  
Alexander Teumer ◽  
Marcus Dörr ◽  
...  
Keyword(s):  
Physical Activity ◽  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Sedentary Behavior ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Artery Disease

Abstract Aims Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke. Methods and results We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke. Conclusions These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased. Graphic abstract

Genetically rheumatoid arthrits and risk of comorbidities: a Mendelian randomization study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Fokina ◽  
J Fill ◽  
G Klappacher
Keyword(s):  
Rheumatoid Arthritis ◽  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Funding Source ◽  
Artery Disease ◽  
Genetically Determined ◽  
Genetic Instruments

Abstract Background Ample observational evidence indicates that patients with rheumatoid arthritis (RA) are at increased risk of developing comorbid conditions, in particular cardiovascular disease. The pathogenesis of these comorbidities is still largely unknown. For effective preventive measures, it would however be important to discriminate between those that are causally linked with rheumatoid arthritis and those that are the results of concomitant treatments or other confounding factors. Purpose Our objective was to explore whether genetically determined manifestation of RA was associated with any comorbidities, in particular cardiovascular disease, by conducting a 2-sample Mendelian randomization (MR) study on publicly available summary statistics from genome-wide association study (GWAS) consortia. Methods Genetic instruments for RA were obtained from a GWAS of 14,361 autoantibody-positive individuals with RA and 43,923 controls of European descent (Okada et al. 2014). The CARDIoGRAMplusC4D consortium comprising 60,801 cases with coronary artery disease and 123,504 controls was used to evaluate the associations with cardiovascular outcomes applying inverse variance–weighted meta-analysis, weighted-median analysis, Mendelian randomization–Egger regression, and multivariable Mendelian randomization. Genetic instruments for RA were further tested for association with other etiologically related traits by using publicly available GWAS data. Results Genetic predisposition to RA was not associated with higher risk of coronary artery disease (beta coefficient [b] ± standard error [se] = 0.02±0.03; P=0.4913), and myocardial infarction (b ± se = 0.03±0.03; P=0.3338). In contrast, IgA nephropathy (b ± se = 0.47±0.18; P=0.0225) and triglyceride levels were significantly related as outcomes to genetically determined RA as exposure. Other significantly related outcomes were the manifestation of squamous cell lung cancer (b ± se = 0.17±0.08; P=0.0496), serous ovarian cancer (b ± se = 0.13±0.05; P=0.0202), and prostate cancer (b ± se = 0.06±0.02; P=0.0041). Conclusions Despite the high prevalence of coronary artery disease and myocardial infarction among RA patients in observational studies, cardiovascular outcomes were not significantly associated with RA by Mendelian randomization. This paradox might partly be explained by the traits such as IgA nephropathy and elevated triglyceride levels that could act as mediators for the increased cardiovascular risk by their causal link with genetically determined RA. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Medical University of Vienna, Austria

scholarly journals Causal associations of insulin resistance with coronary artery disease and ischemic stroke: a Mendelian randomization analysis

2020 ◽  
Vol 8 (1) ◽  
pp. e001217 ◽  
Author(s):  
Weiqi Chen ◽  
Shukun Wang ◽  
Wei Lv ◽  
Yuesong Pan
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Ischemic Stroke ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Artery Occlusion ◽  
Small Artery ◽  
Small Artery Occlusion ◽  
Weighted Median ◽  
Artery Disease

IntroductionThe relationship between insulin resistance (IR) and cardiovascular diseases is unclear. We aimed to examine the causal associations of IR with cardiovascular diseases, including coronary artery disease, myocardial infarction, ischemic stroke and its subtypes, using Mendelian randomization.Research design and methodsDue to low sample size for gold standard measures and in order to well reflect the underlying phenotype of IR, we used 53 single nucleotide polymorphisms associated with IR phenotypes (ie, fasting insulin, high-density lipoprotein cholesterol and triglycerides) from recent genome-wide association studies (GWASs) as instrumental variables. Summary-level data from four GWASs of European individuals were used. Data on IR phenotypes were obtained from meta-analysis of GWASs of up to 188 577 individuals and data on the outcomes from GWASs of up to 446 696 individuals. Mendelian randomization (MR) estimates were calculated with inverse-variance weighted, simple and weighted-median approaches and MR-Egger regression was used to explore pleiotropy.ResultsGenetically predicted 1-SD increase in IR phenotypes were associated with a substantial increase in risk of coronary artery disease (OR=1.79, 95% CI: 1.57 to 2.04, p<0.001), myocardial infarction (OR=1.78, 95% CI: 1.54 to 2.06, p<0.001), ischemic stroke (OR=1.21, 95% CI: 1.05 to 1.40, p=0.007) and the small-artery occlusion subtype of stroke (OR=1.80, 95% CI: 1.30 to 2.49, p<0.001), but not associated with the large-artery atherosclerosis and cardioembolism subtypes of stroke. There was no evidence of pleiotropy. Results were broadly consistent in sensitivity analyses using simple and weighted-median approaches accounting for potential genetic pleiotropy.ConclusionsThis study provides evidence to support that IR was causally associated with risk of coronary artery disease, myocardial infarction, ischemic stroke and the small-artery occlusion subtype of stroke.

scholarly journals Serum Parathyroid Hormone and Risk of Coronary Artery Disease: Exploring Causality Using Mendelian Randomization

2019 ◽  
Vol 104 (11) ◽  
pp. 5595-5600 ◽  
Author(s):  
Håkan Melhus ◽  
Karl Michaëlsson ◽  
Susanna C Larsson
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Parathyroid Hormone ◽  
Coronary Artery ◽  
Mendelian Randomization ◽  
Sensitivity Analyses ◽  
Nucleotide Polymorphisms ◽  
Serum Parathyroid Hormone ◽  
Increased Risk ◽  
Artery Disease

Abstract Context Elevated circulating parathyroid hormone concentrations have been associated with increased risk of cardiovascular disease in observational studies, but whether the association is causal is unknown. Objective We used the Mendelian randomization design to test whether genetically increased serum parathyroid hormone (S-PTH) concentrations are associated with coronary artery disease (CAD). Design, Setting, and Participants Five single-nucleotide polymorphisms robustly associated with S-PTH concentrations were used as instrumental variables to estimate the association of genetically higher S-PTH concentrations with CAD. Summary statistics data for CAD were obtained from a genetic consortium with data from 184,305 individuals (60,801 CAD cases and 123,504 noncases). Main Outcome Measure OR of CAD per genetically predicted one SD increase of S-PTH concentrations. Results Genetically higher S-PTH concentration was not associated with CAD as a whole or myocardial infarction specifically (∼70% of total cases). The ORs per genetically predicted one SD increase in S-PTH concentration were 1.01 (95% CI: 0.93 to 1.09; P = 0.88) for CAD and 1.02 (95% CI: 0.94 to 1.10; P = 0.64) for myocardial infarction. The lack of association remained in various sensitivity analyses. Conclusion Genetic predisposition to higher S-PTH concentrations does not appear to be an independent risk factor for CAD.

scholarly journals Circulating Vitamin E Levels and Risk of Coronary Artery Disease and Myocardial Infarction: A Mendelian Randomization Study

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2153 ◽  
Author(s):  
Tao Wang ◽  
Lin Xu
Keyword(s):  
Myocardial Infarction ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Vitamin E ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Genome Wide ◽  
A Genome ◽  
Artery Disease

Observational studies have reported a cardioprotective effect of vitamin E whereas intervention trials failed to confirm its beneficial effects, and even some reported adverse effects of vitamin E supplements on coronary artery disease (CAD). To clarify, we conducted a two-sample mendelian randomization study to investigate causal association of vitamin E with the risk of CAD. Three single nucleotide polymorphisms (SNPs) identified in a genome-wide analysis study including 7781 individuals of European descent, rs964184, rs2108622, and rs11057830 were used as the genetic instruments for vitamin E. Data for CAD/myocardial infarction (MI) were available from Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics consortium. The effect of each SNP on CAD/myocardial infarction (MI) was weighted by its effect on serum vitamin E (mg/L), and results were pooled to give a summary estimates for the effect of increased vitamin E on risk of CAD/MI. Based on 3 SNPs each 1 mg/L increase in vitamin E was significantly associated with CAD (odds ratio (OR) 1.05, 95% confidence interval (CI) 1.03–1.06), MI (OR 1.04, 95% CI 1.03–1.05), elevated low-density lipoprotein cholesterol (0.021 standard deviations (SD), 95% CI 0.016, 0.027), triglycerides (0.026 SD, 95% CI 0.021, 0.031), and total cholesterol (0.043 SD, 95% CI 0.038, 0.048) and lower levels of high-density lipoprotein cholesterol (−0.019 SD 95% CI −0.024, −0.014). Our findings indicate that higher vitamin E may increase the risk of CAD/MI and the safety and efficacy of vitamin E supplementation use should be reevaluated.

scholarly journals The impact of growth differentiation factor 15 on the risk of cardiovascular disease: evidence from Mendelian randomization study

2020 ◽  
Author(s):  
Zhuo Wang ◽  
Fangkun Yang ◽  
Menghuai Ma ◽  
Qinyi Bao ◽  
Jinlian Shen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Causal Relationship ◽  
Mendelian Randomization ◽  
Cardioembolic Stroke ◽  
Growth Differentiation Factor 15 ◽  
Artery Disease

Abstract Background: Growth differentiation factor 15(GDF-15) concentration is apparently associated with cardiovascular disease, but whether there is a causal relationship has not been testified. Methods: We utilized Mendelian randomization to assess the function of GDF-15 in incidence of cardiovascular disease. The single-nucleotide polymorphism- GDF-15 association evaluations came from meta-analysis of genome-wide association study (GWAS). Besides inverse-variance weighted, MR-Egger test and weighted median method were applied to examine sensitivity. Results: Based on the instruments, GDF-15 level linked to the increasing risk of cardioembolic stroke (OR 1.09 per SD increase, 95% CI 1.01, 1.19) , atrial fibrillation (OR 1.03 per SD increase, 95% CI 1.0, 1.06), coronary artery disease (OR 0.94 per SD increase, 95% CI 0.89, 0.99) and myocardial infarction (OR 0.94 per SD increase, 95% CI 0.90, 0.98). However, the significant causal relationship between GDF-15 and the other cardiovascular diseases was not found in our study. Conclusions: The result suggested that GDF-15 was causally associated with the risk of cardioembolic stroke,atrial fibrillation, coronary artery disease and myocardial infarction, providing us conceivable strategies to alleviate the burden of cardiovascular disease.

scholarly journals The impact of growth differentiation factor 15 on the risk of cardiovascular disease: evidence from Mendelian randomization study

2020 ◽  
Author(s):  
Zhuo Wang ◽  
Fangkun Yang ◽  
Menghuai Ma ◽  
Qinyi Bao ◽  
Jinlian Shen ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Causal Relationship ◽  
Mendelian Randomization ◽  
Cardioembolic Stroke ◽  
Growth Differentiation Factor 15 ◽  
Artery Disease

Abstract Background: Growth differentiation factor 15(GDF-15) concentration is apparently associated with cardiovascular disease, but whether there is a causal relationship has not been testified. Methods: We utilized Mendelian randomization to assess the function of GDF-15 in incidence of cardiovascular disease. The single-nucleotide polymorphism- GDF-15 association evaluations came from meta-analysis of genome-wide association study (GWAS). Besides inverse-variance weighted, MR-Egger test and weighted median method were applied to examine sensitivity. Results: Based on the instruments, GDF-15 level linked to the increasing risk of cardioembolic stroke (1.06, OR 1.09 per SD increase, 95% CI 1.01, 1.19) , atrial fibrillation (OR 1.03 per SD increase, 95% CI 1.0, 1.06), coronary artery disease (OR 0.94 per SD increase, 95% CI 0.89, 0.99) and myocardial infarction (OR 0.94 per SD increase, 95% CI 0.90, 0.98). However, the significant causal relationship between GDF-15 and the other cardiovascular diseases was not found in our study. Conclusions: The result suggested that GDF-15 was causally associated with the risk of cardioembolic stroke,atrial fibrillation, coronary artery disease and myocardial infarction, providing us conceivable strategies to alleviate the burden of cardiovascular disease.

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