As described previously11, specimens from participants in the discovery sample were genotyped using one of three genome-wide SNP arrays: the Illumina HumanOmni1-Quad v1.0 microarray containing 988,306 autosomal SNPs (Yale-Penn 1), the Illumina Infinium Human Core Exome microarray containing 265,919 exonic SNPs and approximately 240,000 tagging SNPs (Yale-Penn 2), and the Illumina Multi-ethnic Global Array containing 1,779,819 markers representing five major populations (Yale-Penn 3). Genotyping was performed at the Yale Center for Genome Analysis, except for a group of 2538 samples (1784 AAs and 754 EAs) that were genotyped at the Center for Inherited Disease Research. Quality control of genotype data was performed as previously described18. Briefly, individuals with a call rate < 98% and variants with minor allele frequency (MAF) < 1% were excluded. Pairwise identity-by-decent (IBD) was calculated with PLINK19 to determine genetic relatedness among individuals in the sample and individuals with a pairwise IBD estimate > 25% were assigned to the same family. Self-reported males with X chromosome heterozygosity > 20% and self-reported females with X chromosome heterozygosity < 20% were excluded. Population substructure in the entire sample
