We applied the methods to test for causal associations between seven health risk factors and common diseases using data from multiple large studies. The risk factors are BMI, waist-to-hip ratio adjusted for BMI (WHRadjBMI), HDL cholesterol (HDL-c), LDL-c, triglycerides (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). We chose these risk factors because of the availability of summary-level GWAS data from large samples (n = 108,039–322,154) (Supplementary Table 3). We accessed data for BMI, WHRadjBMI, HDL-c, LDL-c and TG from published GWAS24–26, and data for SBP and DBP from the subgroup of UK Biobank (UKB)27 with genotyped data released in 2015. We selected SNPs at a genome-wide significance level (PGWAS < 5 × 10–8) using the clumping algorithm (r2 threshold = 0.05 and window size = 1 Mb) implemented in PLINK28 (Methods). Note that the GSMR method accounts for the remaining LD not removed by the clumping analysis. There were m = 84, 43, 159, 141, 101, 28, and 29 SNPs for BMI, WHRadjBMI, HDL-c, LDL-c, TG, SBP and DBP, respectively, after clumping. These SNP instruments are nearly
