Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants
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Citations
Causal Associations Between Circulating Adipokines and Cardiovascular Disease: A Mendelian Randomization Study
Smoking and heart failure: a Mendelian randomization and mediation analysis.
Gout and Metabolic Disease: Investigation of Potential Relationship in the New Zealand Population
Causal relationship between genetically predicted depression and cancer risk: a two-sample bi-directional mendelian randomization
Single-cell expression and Mendelian randomization analyses identify blood genes associated with lifespan and chronic diseases.
References
Measuring inconsistency in meta-analyses
Bias in meta-analysis detected by a simple, graphical test
Principal components analysis corrects for stratification in genome-wide association studies
Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials
‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?
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Frequently Asked Questions (8)
Q2. What is the practical difficulty of determining which variants to include in a mendelian?
A practical difficulty of determining which variants to include in a Mendelian randomization analysis using measured covariates, aside from that of distinguishing between pleiotropy and mediation, is that of multiple testing.
Q3. what is the role of anakinra in reducing interleukin-1 levels?
For instance, inhibition of interleukin-1 by the drug anakinra has been observed to lead to decreased levels of c-reactive protein and interleukin-6 in clinical trials.
Q4. what are the main approaches to assess the association of genetic variants with the risk factor?
if there are covariates that by biological considerations should be downstream consequences of the risk factor, then the associations of genetic variants with these covariates can be assessed as positive controls to give confidence that the function of the genetic variants matches the known consequences of the risk factor.
Q5. What methods allow more general departures from the instrumental variable assumptions for the invalid instruments?
the penalization and median-based methods allow more general departures from the instrumental variable assumptions for the invalid instruments.
Q6. what are the main approaches to assess the association of genetic variants with a measured covari?
23For instance, if increasing body mass index leads to increased blood pressure, then genetic variants that are instrumental variables for body mass index should also be associated with blood pressure.
Q7. what is the pleiotropic effect of the egger regression method?
under an assumption that is weaker than standard instrumental variable assumptions, the slope coefficient from the egger regression method provides an estimate of the causal effect that is consistent asymptotically even if all the genetic variants have pleiotropic effects on the outcome.
Q8. what is the l1 penalization method for cAD?
this approach has been applied for investigating the causal effect of lipid fractions on cAD risk.50 More formal penalizationmethods have been proposed using l1-penalization to downweight the contribution of outlying variants to the analysis in a continuous way.