scholarly journals Dissecting the IL‐6 pathway in cardiometabolic disease: a Mendelian randomization study on both IL6 and IL6R .

2021 ◽  
Author(s):  
Arjen J. Cupido ◽  
Folkert W. Asselbergs ◽  
Pradeep Natarajan ◽  
Paul M. Ridker ◽  
G. Kees Hovingh ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Cardiometabolic Disease

scholarly journals Mendelian randomization in cardiometabolic disease: challenges in evaluating causality

2017 ◽  
Vol 14 (10) ◽  
pp. 577-590 ◽  
Author(s):  
Michael V. Holmes ◽  
Mika Ala-Korpela ◽  
George Davey Smith
Keyword(s):  
Mendelian Randomization ◽  
Cardiometabolic Disease

scholarly journals Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach

PLoS Medicine ◽  
2017 ◽  
Vol 14 (1) ◽  
pp. e1002215 ◽  
Author(s):  
Michael M. Mendelson ◽  
Riccardo E. Marioni ◽  
Roby Joehanes ◽  
Chunyu Liu ◽  
Åsa K. Hedman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Blood Cells ◽  
Mendelian Randomization ◽  
Cardiometabolic Disease

scholarly journals Selection into shift work is influenced by educational attainment and body mass index: A Mendelian randomization study

2020 ◽  
Author(s):  
Iyas Daghlas ◽  
Rebecca C. Richmond ◽  
Jacqueline M. Lane ◽  
Hassan S. Dashti ◽  
Hanna M. Ollila ◽  
...  
Keyword(s):  
Risk Factors ◽  
Body Mass Index ◽  
Educational Attainment ◽  
Body Mass ◽  
Shift Work ◽  
Cardiometabolic Risk ◽  
Mendelian Randomization ◽  
Cardiometabolic Risk Factors ◽  
Cardiometabolic Disease ◽  
Sleep Timing

AbstractBackgroundShift work is associated with increased cardiometabolic disease risk, but whether this association is influenced by cardiometabolic risk factors driving selection into shift work is currently unclear. We addressed this question using Mendelian randomization (MR) in the UK Biobank.MethodsWe created genetic risk scores (GRS) associating with nine cardiometabolic risk factors (including education, body mass index [BMI], smoking, and alcohol consumption), and tested associations of each GRS with self-reported current frequency of shift work and night shift work amongst employed UKB participants of European ancestry (n=190,573). We used summary-level MR sensitivity analyses and multivariable MR to probe robustness of the identified effects, and tested whether effects were mediated through sleep timing preference.ResultsGenetically instrumented lower educational attainment and higher body mass index increased odds of reporting frequent shift work (odds ratio [OR] per 3.6 years [1-SD] decrease in educational attainment=2.40, 95% confidence interval [CI]=2.22-2.59, p=4.84 × 10−20; OR per 4.7kg/m2 [1-SD] increase in BMI=1.30, 95%CI=1.14-1.47, p=5.85 × 10−05). Results were unchanged in sensitivity analyses allowing for different assumptions regarding horizontal pleiotropy, and the effects of education and BMI were independent in multivariable MR. No causal effects were evident for the remaining factors, nor for any exposures on selection out of shift work. Sleep timing preference did not mediate any causal effects.ConclusionsEducational attainment and BMI may influence selection into shift work, which may have implications for epidemiologic associations of shift work with cardiometabolic disease.Key messagesAlthough it has been hypothesized that cardiometabolic risk factors and diseases may influence selection into shift work, little evidence for such an effect is currently available.Using Mendelian randomization, we assessed whether cardiometabolic risk factors and diseases influenced selection into or out of shift work in the UK Biobank.Our results were consistent with a causal effect of both higher BMI and lower educational attainment on selection into current shift work, with stronger effects seen for shift work that is more frequent and includes more night shifts.Using multivariable Mendelian randomization, we found that effects of higher BMI and lower education were independent. Sleep timing preference had a null effect on shift work selection and therefore did not mediate these effects.Selection through education and BMI may bias the relationship of shift work with cardiometabolic disease. Social mechanisms underlying these effects warrant further investigation.

scholarly journals The contribution of tissue-grouped BMI-associated gene sets to cardiometabolic-disease risk: a Mendelian randomization study

2020 ◽  
Vol 49 (4) ◽  
pp. 1246-1256
Author(s):  
Inge Verkouter ◽  
Renée de Mutsert ◽  
Roelof A J Smit ◽  
Stella Trompet ◽  
Frits R Rosendaal ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Mendelian Randomization ◽  
Disease Risk ◽  
Expression Profiles ◽  
Association Studies ◽  
Tissue Expression ◽  
Cardiometabolic Disease ◽  
Genome Wide Association Studies ◽  
Gene Sets ◽  
Artery Disease

Abstract Background Body mass index (BMI)-associated loci are used to explore the effects of obesity using Mendelian randomization (MR), but the contribution of individual tissues to risks remains unknown. We aimed to identify tissue-grouped pathways of BMI-associated loci and relate these to cardiometabolic disease using MR analyses. Methods Using Genotype-Tissue Expression (GTEx) data, we performed overrepresentation tests to identify tissue-grouped gene sets based on mRNA-expression profiles from 634 previously published BMI-associated loci. We conducted two-sample MR with inverse-variance-weighted methods, to examine associations between tissue-grouped BMI-associated genetic instruments and type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD), with use of summary-level data from published genome-wide association studies (T2DM: 74 124 cases, 824 006 controls; CAD: 60 801 cases, 123 504 controls). Additionally, we performed MR analyses on T2DM and CAD using randomly sampled sets of 100 or 200 BMI-associated genetic variants. Results We identified 17 partly overlapping tissue-grouped gene sets, of which 12 were brain areas, where BMI-associated genes were differentially expressed. In tissue-grouped MR analyses, all gene sets were similarly associated with increased risks of T2DM and CAD. MR analyses with randomly sampled genetic variants on T2DM and CAD resulted in a distribution of effect estimates similar to tissue-grouped gene sets. Conclusions Overrepresentation tests revealed differential expression of BMI-associated genes in 17 different tissues. However, with our biology-based approach using tissue-grouped MR analyses, we did not identify different risks of T2DM or CAD for the BMI-associated gene sets, which was reflected by similar effect estimates obtained by randomly sampled gene sets.

scholarly journals The Contribution Of Tissue-Specific Bmi-Associated Gene Sets To Cardiometabolic Disease Risk Using Mendelian Randomization

2019 ◽  
Vol 287 ◽  
pp. e69-e70
Author(s):  
I. Verkouter ◽  
R. de Mutsert ◽  
R. Smit ◽  
F. Rosendaal ◽  
D. van Heemst ◽  
...  
Keyword(s):  
Mendelian Randomization ◽  
Disease Risk ◽  
Cardiometabolic Disease ◽  
Tissue Specific ◽  
Gene Sets ◽  
Cardiometabolic Disease Risk
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