Each study conducted single marker association analyses assuming an additive genetic model taking genotype imputation uncertainty into account. Analyses were stratified by sex (except for studies with related individuals where analyses accounted for family structure) and disease status for studies that ascertained participants based on a relevant disease (e.g., diabetes). Before meta-analyzing data, results from each study were extensively reviewed using standardized quality control procedures to identify potential problems, such as strand issues, discrepancies between the reported standard errors and p-values, and allele frequency differences. SNPs with poor imputation quality scores or estimated minor allele count ≤ 20 (i.e. 2 × N × minor allele frequency) in each stratum (men/women or pooled for family-based studies) of each study were removed from analysis. For the discovery stage 1, each stratum- and study-specific GWAS was corrected for genomic control. Meta-analyses were performed for each phenotype in METAL48 using the fixed effects inverse variance method based on the β estimates and standard errors from each study. The results of the discovery meta-analysis were followed by an additional genomic control correction. Similar methods were employed for the replication and joint discovery and replication analysis.
