scholarly journals Coffee Consumption and Cardiovascular Diseases: A Mendelian Randomization Study

Nutrients ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 2218
Author(s):  
Shuai Yuan ◽  
Paul Carter ◽  
Amy M. Mason ◽  
Stephen Burgess ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Intracerebral Hemorrhage ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Uk Biobank ◽  
The Uk

Coffee consumption has been linked to a lower risk of cardiovascular disease in observational studies, but whether the associations are causal is not known. We conducted a Mendelian randomization investigation to assess the potential causal role of coffee consumption in cardiovascular disease. Twelve independent genetic variants were used to proxy coffee consumption. Summary-level data for the relations between the 12 genetic variants and cardiovascular diseases were taken from the UK Biobank with up to 35,979 cases and the FinnGen consortium with up to 17,325 cases. Genetic predisposition to higher coffee consumption was not associated with any of the 15 studied cardiovascular outcomes in univariable MR analysis. The odds ratio per 50% increase in genetically predicted coffee consumption ranged from 0.97 (95% confidence interval (CI), 0.63, 1.50) for intracerebral hemorrhage to 1.26 (95% CI, 1.00, 1.58) for deep vein thrombosis in the UK Biobank and from 0.86 (95% CI, 0.50, 1.49) for subarachnoid hemorrhage to 1.34 (95% CI, 0.81, 2.22) for intracerebral hemorrhage in FinnGen. The null findings remained in multivariable Mendelian randomization analyses adjusted for genetically predicted body mass index and smoking initiation, except for a suggestive positive association for intracerebral hemorrhage (odds ratio 1.91; 95% CI, 1.03, 3.54) in FinnGen. This Mendelian randomization study showed limited evidence that coffee consumption affects the risk of developing cardiovascular disease, suggesting that previous observational studies may have been confounded.

scholarly journals Serum calcium and 25-hydroxyvitamin D in relation to longevity, cardiovascular disease and cancer: a Mendelian randomization study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Shuai Yuan ◽  
John A. Baron ◽  
Karl Michaëlsson ◽  
Susanna C. Larsson
Keyword(s):  
Cardiovascular Disease ◽  
Serum Calcium ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Genome Wide Association ◽  
Uk Biobank ◽  
Hydroxyvitamin D ◽  
Genome Wide ◽  
25 Hydroxyvitamin D ◽  
The Uk

AbstractAssociations of serum calcium (S-Ca) and 25-hydroxyvitamin D (S-25(OH)D) concentrations with longevity, cardiovascular disease, and cancer are not clear. We conducted a Mendelian randomization study to examine the associations of S-Ca and S-25(OH)D with longevity and risk of cardiovascular disease and cancer. The primary genetic instruments for S-Ca and S-25(OH)D were obtained from genome-wide association meta-analyses that included 61,054 individuals for S-Ca and up to 79,366 individuals for S-25(OH)D. Genetic variants associated with S-Ca and S-25(OH)D in the UK Biobank were used as confirmatory instruments. We obtained summary-level data for associations of these instruments with individual survival later than the 90th versus at most the 60th percentile of expected age at death from a genome-wide association meta-analysis including 11,262 cases and 25,483 controls, and with parental longevity (both parents in top 10% percentile) from the UK Biobank including 7,182 cases and 79,767 controls. Data for cardiovascular disease (111,108 cases and 107,684 controls) and cancer (38,036 cases and 180,756 controls) were obtained from the FinnGen consortium. A one standard deviation increase in genetically-predicted S-Ca concentration was associated with lower odds of longevity (odds ratio, 0.72; 95% CI, 0.55-0.95) and increased risk of cardiovascular disease (odds ratio, 1.11; 95% CI, 1.03-1.20). The associations were consistent in confirmatory analyses. There was no evidence supporting an association between genetically-predicted S-Ca and cancer, and no associations of genetically-predicted S-25(OH)D with the studied outcomes. Lifelong higher levels of S-Ca but not S-25(OH)D may shorten life expectancy and increase the risk of cardiovascular disease.

Abstract P147: Genome Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Diseases Using the UK Biobank Data

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Yanjun Guo ◽  
Wonil Chung ◽  
Zhilei Shan ◽  
Liming Liang
Keyword(s):  
Cardiovascular Diseases ◽  
Genetic Correlation ◽  
Multiple Testing ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk ◽  
Cardiovascular Traits ◽  
Shared Genetic

Background: Patients with RA have a 2-10 folds increased risk of cardiovascular diseases (CVD) and CVD accounts for almost 50% of the excess mortality in patients with RA when compared with general population, but the mechanisms underlying such associations are largely unknown. Methods: We examined the genetic correlation, causality, and shared genetic variants between RA (Ncase=6,756, Ncontrol=452,476) and CVD (Ncase=44,246, Ncontrol=414,986) using LD Score regression (LDSC), generalized summary-data-based Mendelian Randomization (GSMR), and cross-trait meta-analysis in the UK Biobank Data. Results: In the present study, RA was significantly genetically correlated with MI, angina, CHD, and CVD after correcting for multiple testing (Rg ranges from 0.40 to 0.43, P<0.05/5). Interestingly, when stratified by frequent usage of aspirin and paracetamol, we observed increased genetic correlation between RA and CVD for participants without aspirin usage ( Rg increased to 0.54 [95%CI: 0.54, 0.78] for angina; P value=6.69х10 -6 ), and for participants with usage of paracetamol ( Rg increased to 0.75 [95%CI: 0.20, 1.29] for MI; P value=8.90х10 -3 ). Cross-trait meta-analysis identified 9 independent loci that were shared between RA and at least one of the genetically correlated CVD traits including PTPN22 at chr1p13.2 , BCL2L11 at chr2q13 , and CCR3 at chr3p21.31 ( P single trait <1х10 -3 and P meta <5х10 -8 ) highlighting potential shared etiology between them which include accelerating atherosclerosis and upregulating oxidative stress and vascular permeability. Finally, Mendelian randomization analyses observed inconsistent instrumental effects and were unable to conclude the causality and directionality between RA and CVD. Conclusion: Our results supported positive genetic correlation between RA and multiple cardiovascular traits, and frequent usage of aspirin and paracetamol may modify their associations, but instrumental analyses were unable to conclude the causality and directionality between them.

scholarly journals Causal associations between COVID-19 and Atrial Fibrillation: A bidirectional Mendelian randomization study

2020 ◽  
Author(s):  
Xiaoyu Zhang ◽  
Biyan Wang ◽  
Di Liu ◽  
Jinxia Zhang ◽  
Qiuyue Tian ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Disease ◽  
High Risk ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
The Elderly ◽  
Biological Pathway ◽  
Limited Evidence

Abstract Background Observational studies showed that coronavirus disease 2019 (COVID-19) attacks universally and its most menacing progression uniquely endangers the elderly with cardiovascular disease (CVD). Whether COVID-19 is causally related to increasing susceptibility and severity of atrial fibrillation (AF), the main form of CVD, remains still unknown. Methods The study aims to investigate the bidirectional causal relations of COVID-19 with AF using two-sample Mendelian randomization (MR) analysis. Results MR evidence suggested genetically predicted severe COVID-19 was significantly associated with higher risk of AF (odds ratio [OR], 1.041; 95% confidence interval (CI), 1.007-1.076; P = 0.017), while genetically predicted AF was not causally associated with severe COVID-19 (OR, 0.831; 95% CI, 1.619-1.115; P=0.217). There was limited evidence to support association of genetically proxied COVID-19 with risk of AF (OR, 1.051; 95% CI, 0.991-1.114; P=0.097), and vice versa (OR, 0.163; 95% CI, 0.004-6.790; P=0.341). MR-Egger indicated no evidence of pleiotropic bias. Conclusion Overall, severe COVID-19 may causally affect AF through independent biological pathway. Survivors from severe COVID-19 might be of high risk of AF in the future. Key words Coronavirus disease 2019; Atrial Fibrillation; Bidirectional mendelian randomization

scholarly journals Association between Alzheimer's disease and COVID-19: A bidirectional Mendelian randomization

2020 ◽  
Author(s):  
Di Liu ◽  
Xiaoyu Zhang ◽  
Weijie Cao ◽  
Jie Zhang ◽  
Manshu Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Confidence Interval ◽  
Genetic Variants ◽  
Odds Ratio ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
Biological Pathways ◽  
Bidirectional Regulation ◽  
Increased Risk

Background In observational studies, Alzheimer's disease (AD) has been associated with an increased risk of Coronavirus disease 2019 (COVID-19), and the prognosis of COVID-19 can affect nervous systems. However, the causality between these conditions remains to be determined. Methods This study sought to investigate the bidirectional causal relations of AD with COVID-19 using two-sample Mendelian randomization (MR) analysis. Results We found that genetically predicted AD was significantly associated with higher risk of severe COVID-19 (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.139-9.725; P=0.028). It's interesting that genetically predicted severe COVID-19 was also significantly associated with higher risk of AD (OR, 1.004; 95% CI, 1.001-1.007; P=0.018). In addition, the two strong genetic variants associated with severe COVID-19 was associated with higher AD risk (OR, 1.018; 95% CI, 1.003-1.034; P=0.018). There is no evidence to support that genetically predicted AD was significantly associated with COVID-19 susceptibility, and vice versa. No obvious pleiotropy bias and heterogeneity were observed. Conclusion Overall, AD may causally affect severe COVID-19, and vice versa, performing bidirectional regulation through independent biological pathways.

scholarly journals Association between coffee consumption and overall risk of being diagnosed with or dying from cancer among >300 000 UK Biobank participants in a large-scale Mendelian randomization study

2019 ◽  
Vol 48 (5) ◽  
pp. 1447-1456 ◽  
Author(s):  
Jue-Sheng Ong ◽  
Matthew H Law ◽  
Jiyuan An ◽  
Xikun Han ◽  
Puya Gharahkhani ◽  
...  
Keyword(s):  
Cancer Risk ◽  
Observational Studies ◽  
Large Scale ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Cancer Death ◽  
Uk Biobank ◽  
Coffee Intake ◽  
Summary Data ◽  
Overall Risk

Abstract Background Previous observational studies have suggested that coffee intake may be associated with a reduction in cancer risk. Mendelian randomization (MR) studies can help clarify whether the observed associations are likely to be causal. Here we evaluated whether coffee intake is associated with: (i) overall risk of being diagnosed with/dying from any cancer; and (ii) risk of individual cancers. Methods We identified 46 155 cases (of which 6998 were fatal) and 270 342 controls of White British ancestry from the UK Biobank cohort (UKB), based on ICD10 diagnoses. Individuals with benign tumours were excluded. Coffee intake was self-reported and recorded based on cup/day consumption. We conducted both observational and summary data MR analyses. Results There was no observational association between coffee intake and overall cancer risk [odds ratio (OR) per one cup/day increase = 0.99, 95% confidence interval (CI) 0.98, 1.00] or cancer death (OR = 1.01, 0.99, 1.03); the estimated OR from MR is 1.01 (0.94, 1.08) for overall cancer risk and 1.11 (0.95, 1.31) for cancer death. The relationship between coffee intake and individual cancer risks were consistent with a null effect, with most cancers showing little or no associations with coffee. Meta-analysis of our MR findings with publicly available summary data on various cancers do not support a strong causal relationship between coffee and risk of breast, ovarian, lung or prostate cancer, upon correction for multiple testing. Conclusions Taken together, coffee intake is not associated with overall risk of being diagnosed with or dying from cancer in UKB. For individual cancers, our findings were not statistically inconsistent with earlier observational studies, although for these we were unable to rule out a small effect on specific types of cancer.

scholarly journals Does Obesity Cause Thyroid Cancer? A Mendelian Randomization Study

2020 ◽  
Vol 105 (7) ◽  
pp. e2398-e2407
Author(s):  
Jonathan Mark Fussey ◽  
Robin N Beaumont ◽  
Andrew R Wood ◽  
Bijay Vaidya ◽  
Joel Smith ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Thyroid Cancer ◽  
Thyroid Disease ◽  
Observational Studies ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Uk Biobank ◽  
Reverse Causality ◽  
The Uk

Abstract Background The incidence of thyroid cancer is rising, and relatively little is known about modifiable risk factors for the condition. Observational studies have suggested a link between adiposity and thyroid cancer; however, these are subject to confounding and reverse causality. Here, we used data from the UK Biobank and Mendelian randomization approaches to investigate whether adiposity causes benign nodular thyroid disease and differentiated thyroid cancer. Methods We analyzed data from 379 708 unrelated participants of European ancestry in the UK Biobank and identified 1812 participants with benign nodular thyroid disease and 425 with differentiated thyroid carcinoma. We tested observational associations with measures of adiposity and type 2 diabetes mellitus. One and 2-sample Mendelian randomization approaches were used to investigate causal relationships. Results Observationally, there were positive associations between higher body mass index (odds ratio [OR], 1.15; 95% confidence interval [CI], 1.08-1.22), higher waist-hip ratio (OR, 1.16; 95% CI, 1.09-1.23), and benign nodular thyroid disease, but not thyroid cancer. Mendelian randomization did not support a causal link for obesity with benign nodular thyroid disease or thyroid cancer, although it did provide some evidence that individuals in the highest quartile for genetic liability of type 2 diabetes had higher odds of thyroid cancer than those in the lowest quartile (OR, 1.45; CI, 1.11-1.90). Conclusions Contrary to the findings of observational studies, our results do not confirm a causal role for obesity in benign nodular thyroid disease or thyroid cancer. They do, however, suggest a link between type 2 diabetes and thyroid cancer.

scholarly journals Cardiometabolic risk factors for COVID-19 susceptibility and severity: A Mendelian randomization analysis

PLoS Medicine ◽  
2021 ◽  
Vol 18 (3) ◽  
pp. e1003553
Author(s):  
Aaron Leong ◽  
Joanne B. Cole ◽  
Laura N. Brenner ◽  
James B. Meigs ◽  
Jose C. Florez ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Statistical Significance ◽  
Epidemiological Studies ◽  
Population Based ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
The Uk

Background Epidemiological studies report associations of diverse cardiometabolic conditions including obesity with COVID-19 illness, but causality has not been established. We sought to evaluate the associations of 17 cardiometabolic traits with COVID-19 susceptibility and severity using 2-sample Mendelian randomization (MR) analyses. Methods and findings We selected genetic variants associated with each exposure, including body mass index (BMI), at p < 5 × 10−8 from genome-wide association studies (GWASs). We then calculated inverse-variance-weighted averages of variant-specific estimates using summary statistics for susceptibility and severity from the COVID-19 Host Genetics Initiative GWAS meta-analyses of population-based cohorts and hospital registries comprising individuals with self-reported or genetically inferred European ancestry. Susceptibility was defined as testing positive for COVID-19 and severity was defined as hospitalization with COVID-19 versus population controls (anyone not a case in contributing cohorts). We repeated the analysis for BMI with effect estimates from the UK Biobank and performed pairwise multivariable MR to estimate the direct effects and indirect effects of BMI through obesity-related cardiometabolic diseases. Using p < 0.05/34 tests = 0.0015 to declare statistical significance, we found a nonsignificant association of genetically higher BMI with testing positive for COVID-19 (14,134 COVID-19 cases/1,284,876 controls, p = 0.002; UK Biobank: odds ratio 1.06 [95% CI 1.02, 1.10] per kg/m2; p = 0.004]) and a statistically significant association with higher risk of COVID-19 hospitalization (6,406 hospitalized COVID-19 cases/902,088 controls, p = 4.3 × 10−5; UK Biobank: odds ratio 1.14 [95% CI 1.07, 1.21] per kg/m2, p = 2.1 × 10−5). The implied direct effect of BMI was abolished upon conditioning on the effect on type 2 diabetes, coronary artery disease, stroke, and chronic kidney disease. No other cardiometabolic exposures tested were associated with a higher risk of poorer COVID-19 outcomes. Small study samples and weak genetic instruments could have limited the detection of modest associations, and pleiotropy may have biased effect estimates away from the null. Conclusions In this study, we found genetic evidence to support higher BMI as a causal risk factor for COVID-19 susceptibility and severity. These results raise the possibility that obesity could amplify COVID-19 disease burden independently or through its cardiometabolic consequences and suggest that targeting obesity may be a strategy to reduce the risk of severe COVID-19 outcomes.

scholarly journals Association of genetically predicted serum estradiol with risk of thromboembolism in men: A mendelian randomization study

2021 ◽  
Author(s):  
Maria Nethander ◽  
Johan Quester ◽  
Liesbeth Vandenput ◽  
Claes Ohlsson
Keyword(s):  
Ischemic Stroke ◽  
Odds Ratio ◽  
Mendelian Randomization ◽  
Causal Role ◽  
Gene Region ◽  
Uk Biobank ◽  
Increased Risk ◽  
Self Reports ◽  
The Uk

Abstract Context An association was recently reported between genetic markers related to high testosterone and increased risk of thromboembolism in men but a possible causal role of estradiol for risk of thromboembolism in men remains unknown. Objective To determine whether endogenous estradiol has a causal role in thromboembolism in men. Design Two-sample mendelian randomization study using gene-based genetic instruments Setting UK Biobank Participants We assessed the association between endogenous estradiol genetically predicted by 22 variants in the CYP19A1 gene region and risk of thromboembolism (5815 cases) in 170,593 unrelated men of white ancestry in the UK Biobank. Main Outcome Measure Thromboembolism based on self-reports, hospital episodes, and death. Results Endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with risk of thromboembolism (odds ratio per SD increase in estradiol 0.74, 95% confidence interval 0.62-0.90). In contrast, genetic variants in the JMJD1C gene, used as a predictor of high endogenous testosterone, were associated with an increased risk of thromboembolism (odds ratio per SD increase in testosterone 1.39, 1.12-1.72). Subsequent explorative analyses evaluating potential repercussions of thromboembolism revealed that endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with risk of ischemic stroke (0.68, 0.49-0.95) but not myocardial infarction (0.97, 0.84-1.13). Conclusions Genetically predicted estradiol was inversely associated with risk of thromboembolism and ischemic stroke in men. The ratio between testosterone and estradiol, determined by aromatase (CYP19A1) activity, may contribute to the overall impact of sex steroids on thromboembolism in men.

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