To control for false positive associations due to inflated test statistics we evaluated the effectiveness of the primary technical and genomic quality control parameters on the genome-wide inflation of test statistics using the lambda GC (median)56 and as necessary made the QC parameters more stringent until this value was between 0.981 and 1.173 (before inclusion of principal components as covariates) and/or between 0.977 and 1.068 after inclusion of PCA covariates. Additionally, we applied loose PCA filters for strongly stratified datasets even if we did not observe strong inflation of test statistics to retrieve reliable test statistics (Figure S1 shows PCA plots for all cohorts). Since the core PGC cohorts came from many distinct centres, countries, and continents, various measures (e.g., tightening of the technical QC parameters and/or genomic quality control) had to be taken in an iterative process to achieve this goal.
