Genotyping and quality control
The methods for genotyping and quality control for the KARE GWAS have been described elsewhere [5]. For the HEXA GWAS, genomic DNA was extracted from 4,302 participants from an urban cohort and genotyped with Affymetrix Genome-Wide Human SNP array 6.0 (Affymetrix, Inc., Santa Clara, CA, USA). From 4,302 genotyped samples, we excluded samples with a low call rate (≥ 95%, n = 443), high heterozygosity (n = 25), outliers (n = 26), and gender inconsistencies (n = 8), and those obtained from individuals who had developed any kind of cancer (n = 61) were excluded from subsequent analyses, along with related or identical individuals whose computed average pairwise identity-by-state value was higher than that estimated from cryptic first-degree relatives of samples (n = 33). SNP markers with a high missing genotype rate (> 5%), minor allele frequency (MAF) (< 0.01), and significant deviation from Hardy-Weinberg equilibrium (p < 1 × 10-6) were excluded, leaving a total of 627,659 markers to be examined in 3,703 individuals.