Extended Data Fig. 8: Plots for Anti-hypertensive Drug Target MR using cis-pQTL Data.

Inverse variance-weighted MR (Mendelian randomization) was conducted for anti-hypertensive drug target Mendelian randomization using cis-acting pQTLs (n = 35559) as the exposure with five vascular dementia outcomes; WMH (white matter hyperintensities, n = 50559), iFA (inversed fractional anisotropy, n = 31125), MD (mean diffusivity, n = 31147), LS (lacunar stroke, n = 6030/248929 cases/controls), VaD (vascular dementia diagnosis, n = 7008/899672 cases/controls). CAD (coronary artery disease, n = 122733/424528 cases/controls), stroke (n = 67162/454450), and heart failure (Heart Fail., n = 14262/471898 cases/controls) were used as a positive control and are indicated in red. Data are presented as the causal MR estimate as the centre and error bars indicating a +/- a 95% confidence interval (CI), with the minima corresponding to the lower 95% CI bound and the maxima representing the upper 95% CI bound. The number of instrumental variables (IVs) used in each analysis is given, for targets with multiple IVs inverse-variance weighted MR was used, for those with a single IV the Wald ratio was calculated. The F-statistic (Fstat) is also provided as a measure of instrument strength. Pval denotes uncorrected p-values; multiple-comparison corrected p-values (applied at differing levels) are available in the supplement. If the WMH meta-analysis dataset could not be used, the UK-Biobank only WMH dataset is presented instead (indicated by a * next to the IVs). SD (standard deviation), pQTL (protein quantitative trait loci).