The association analysis was conducted stratifying each cohort by ancestry (i.e., African and European ancestries) and genotyping array. For case–control studies, imputed dosages were entered in a logistic regression. For family-based studies, logistic mixed models were used to analyze hard-called best-guess genotypes. The association analyses were adjusted for sex and the within-ancestry top 10 principal components to account for possible confounding by population stratification. To investigate differences between OE and OD, three phenotype definitions were considered: i) OD cases vs. OE controls (ODexposed; n=4,503 and 4,173, respectively); ii) OD cases vs. OU controls (ODunexposed; n=4,238 and 17,700, respectively; iii) OE controls vs. OU controls (OEcontrols; n=4,173 and 32,500). As explained in the Supplementary Methods, we removed some of the cohorts from the ODunexposed meta-analysis due to the deflation (λGC<0.9) caused by the low number of cases and the small case-control ratio. For each phenotype, meta-analyses of the results across the different cohorts were conducted in METAL with weights proportional to the square-root of the sample size for each study22. The effective sample size of each cohort was calculated based on
