The GWAS in UKB were conducted with linear mixed models (BOLT-LMM version 2.3.2) and were adjusted for sex, birth year, sex-specific birth-year dummies, genotyping array and batch, and 40 genetic principal components (PCs) estimated with FlashPCA2 (version 2.0). Two partly overlapping hold-out subsamples of UKB participants were excluded from all single-phenotype GWAS summary statistics that included UKB data, and the participants were instead retained as a hold-out sample for polygenic score analyses (Supplementary Information section 2.3.2). Genetic relatives (pairwise KING coefficient ≥ 0.0442, version 2.1.5) of the held-out individuals were excluded from the study altogether to ensure independence between the discovery and follow-up analyses. In summary, whenever an existing GWAS (or GWAS meta-analysis) was based on UKB, we re-conducted it using the same phenotype definition to generate summary statistics that excluded the hold-out sample and their genetic relatives.
