Mendelian Randomization: Practicum

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Mendelian Randomization: Practicum David Evans Camelia Minică

Applied research question: Does having higher proinflammatory CRP causally increase your blood pressure? Observational analyses (simple linear regressions in R) MR/IV Analyses: Wald Estimator (simple linear regression) MR/IV Analyses: TSLS (AER-package) Manual TSLS (simple linear regression) Weak instrument bias

Applied research question: Does having higher proinflammatory CRP causally increase your blood pressure? HDL, income rs3091244 CRP SBP

Applied research question: Does having higher proinflammatory CRP causally increase your blood pressure? Why: to get a grip on the data, look at the MR assumptions Observational analyses (simple linear regressions in R) a. CRP-SBP OLS association b. SNP rs3091244 – CRP association c. confounders’ (HDL, Income) effect on CRP & SBP d. comparison unadjusted and covariate-adjusted OLS observational CRP-SBP regressions e. conclude

Applied research question: Does having higher proinflammatory CRP causally increase your blood pressure? Why: 1st MR/IV method to test causality 2. MR/IV Analyses: Wald Estimator (simple linear regressions) a. compute the causal effect using the Wald estimator b. compare Wald with the observational OLS of CRP-SBP

Applied research question: Does having higher proinflammatory CRP causally increase your blood pressure? Why: 2nd method to test causality 3. MR/IV Analyses: TSLS (AER R-package) # General format for TSLS command: # summary(ivreg(Outcome~Exposure | Instrument))

4. Manual TSLS (two stage least squares) Stage1: regress CRP on SNP Applied research question: Does having higher proinflammatory CRP causally increase your blood pressure? Why: 2nd method to test causality - TSLS how does it work? 4. Manual TSLS (two stage least squares) Stage1: regress CRP on SNP Stage2: use predicted CRP (predicted_CRP <- predict(Stage1)) to predict SBP

Applied research question: Does having higher proinflammatory CRP causally increase your blood pressure? 5. Weak instrument bias: an issue ?

Applied research question: Does having higher proinflammatory CRP causally increase your blood pressure? Steps: Copy the data, the scripts and the ppt mkdir MRpractical cp -r /faculty/camelia/2017/friday/* MRpractical 2. Run the analyses as described in the ppt & the R-script (easy/difficult) 3. Go to mr.surge.sh to provide your answers (10 MC questions) 4. As you’re running the commands, fill in the graphical representation of the IV analysis with the appropriate variables and beta-coefficient

Applied research question: Does having higher proinflammatory CRP causally increase your blood pressure? Observational analyses (simple linear regressions in R) MR/IV Analyses: Wald Estimator (simple linear regression) MR/IV Analyses: TSLS (AER-package) Manual TSLS (simple linear regression) Weak instrument bias