scholarly journals Causal Factors for Knee, Hip, and Hand Osteoarthritis: A Mendelian Randomization Study in the UK Biobank

2019 ◽  
Vol 71 (10) ◽  
pp. 1634-1641 ◽  
Author(s):  
Thomas Funck‐Brentano ◽  
Maria Nethander ◽  
Sofia Movérare‐Skrtic ◽  
Pascal Richette ◽  
Claes Ohlsson
Keyword(s):  
Mendelian Randomization ◽  
Hand Osteoarthritis ◽  
Uk Biobank ◽  
Causal Factors ◽  
The Uk

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.

Causal Association Between Atopic Dermatitis and Inflammatory Bowel Disease: A 2-Sample Bidirectional Mendelian Randomization Study

2021 ◽  
Author(s):  
Christa Meisinger ◽  
Dennis Freuer
Keyword(s):  
Inflammatory Bowel Disease ◽  
Atopic Dermatitis ◽  
Bowel Disease ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
The Other ◽  
Uk Biobank ◽  
Inflammatory Bowel ◽  
The Uk

Abstract Background Observational studies postulated an association between atopic dermatitis (AD) and inflammatory bowel disease (IBD). However, it remains unclear whether this relationship is causal. Methods To determine whether AD is causally related to IBD and vice versa, a 2-sample Mendelian randomization study was conducted. Independent genetic instruments from the largest available genome-wide association study for AD (EAGLE eczema consortium without the 23andMe study including 10,788 cases and 30,047 controls) were used to investigate the association with IBD in the UK Biobank study (7045 cases, 456,327 controls) and a second European IBD sample (12,882 cases, 21,770 controls). Results Atopic dermatitis was strongly associated with higher risk of IBD as a whole (odds ratio [OR], 1.107; 95% confidence interval [CI], 1.035; 1.183; P = .003) in the UK Biobank study. The positive association was not significant in the other IBD study (OR, 1.114; 95% CI, 0.956; 1.298), but in meta-analyses of results from the 2 studies, the strong association could be confirmed (OR, 1.11; 95% CI, 1.04; 1.18). When evaluating the causal relationship in the other direction, IBD as a whole did not show an association with AD. Subtype analyses revealed that AD was suggestively associated with ulcerative colitis (UC; OR, 1.149; 95% CI, 1.018; 1.297) but not Crohn’s disease (CD). However, there was a suggestive association between CD and AD (OR, 1.034; 95% CI, 1.004; 1.064) but not UC and AD. Conclusions This study supports a causal effect between AD and IBD—but not between IBD and AD. There seems to be considerable differences between UC and CD regarding their specific associations with AD. These findings have implications for the management of IBD and AD in clinical practice.

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 Alcohol consumption and mate choice in UK Biobank: comparing observational and Mendelian randomization estimates

2018 ◽  
Author(s):  
Laurence J Howe ◽  
Daniel J Lawson ◽  
Neil M Davies ◽  
Beate St. Pourcain ◽  
Sarah J Lewis ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Alcohol Use ◽  
Mate Selection ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
Relationship Length ◽  
Spousal Concordance ◽  
Unit Increase ◽  
Related Variant ◽  
The Uk

AbstractAlcohol use is correlated within spouse-pairs, but it is difficult to disentangle the effects of alcohol consumption on mate-selection from social factors or cohabitation leading to spouses becoming more similar over time. We hypothesised that genetic variants related to alcohol consumption may, via their effect on alcohol behaviour, influence mate selection.Therefore, in a sample of over 47,000 spouse-pairs in the UK Biobank we utilised a well-characterised alcohol related variant, rs1229984 in ADH1B, as a genetic proxy for alcohol use. We compared the phenotypic concordance between spouses for self-reported alcohol use with the association between an individual’s self-reported alcohol use and their partner’s rs1229984 genotype using Mendelian randomization. This was followed up by an exploration of the spousal genotypic concordance for the variant and an analysis determining if relationship length may be related to spousal alcohol behaviour similarities.We found strong evidence that both an individual’s self-reported alcohol consumption and rs1229984 genotype are associated with their partner’s self-reported alcohol use. The Mendelian randomization analysis found that each unit increase in an individual’s weekly alcohol consumption increased their partner’s alcohol consumption by 0.26 units (95% C.I. 0.15, 0.38; P=1.10×10-5). Furthermore, the rs1229984 genotype was concordant within spouse-pairs, suggesting that some spousal concordance for alcohol consumption existed prior to cohabitation. Although the SNP is strongly associated with ancestry, our results suggest that this concordance is unlikely to be explained by population stratification. Overall, our findings suggest that alcohol behaviour directly influences mate selection.

scholarly journals Alcohol use and cardiometabolic risk in the UK Biobank: a Mendelian randomization study

2020 ◽  
Author(s):  
Joanna Lankester ◽  
Daniela Zanetti ◽  
Erik Ingelsson ◽  
Themistocles L. Assimes
Keyword(s):  
Type 2 Diabetes ◽  
Alcohol Consumption ◽  
Alcohol Use ◽  
Mendelian Randomization ◽  
Lower Amount ◽  
Cardiometabolic Health ◽  
Uk Biobank ◽  
The Uk ◽  
Cardiometabolic Traits

AbstractObservational studies suggest alcohol use promotes the development of some adverse cardiometabolic traits but protects against others including outcomes related to coronary artery disease. We used Mendelian randomization to explore causal relationships between the degree of alcohol consumption and several cardiometabolic traits in the UK Biobank. We found carriers of the ADH1B Arg47His variant (rs1229984) reported a 26% lower amount of alcohol consumption compared to non-carriers. In our one-sample, two-stage least squares analyses of the UK Biobank using rs1229984 as an instrument, one additional drink/day was associated with statistically significant elevated level of systolic blood pressure (3.0 mmHg), body mass index (0.87 kg/m^2), waist circumference (1.3 cm), body fat percentage (1.7%), low-density lipoprotein levels in blood (0.16 mmol/L), and the risk of myocardial infarction (OR=1.50), stroke (OR=1.52), any cardiovascular disease (OR=1.43), and all-cause mortality (OR=1.41). Conversely, increasing use of alcohol was associated with reduced levels of triglycerides (−0.059 mmol/L) and HbA1C (−0.42 mmol/mol) in the blood, the latter possibly a consequence of a statistically elevated mean corpuscular volume among ADH1B Arg47His carriers. Stratifications by sex and smoking revealed a pattern of more harm of alcohol use among men compared to women, but no consistent difference by smoking status. Men had an increased risk of heart failure (OR = 1.76), atrial fibrillation (OR = 1.35), and type 2 diabetes (OR = 1.31) per additional drink/day. Using summary statistics from external datasets in 2-sample analyses for replication, we found causal associations between alcohol and obesity, stroke, ischemic stroke, and type 2 diabetes. Our results are consistent with an overall harmful effect of alcohol on cardiometabolic health at all levels of use and suggest that even moderate alcohol use should not be promoted as a part of a healthy diet and lifestyle.

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