Genotyping

Genotyping in the ARIC Study was performed using the Affymetrix genome-wide Human SNP Array 6.0. Extensive quality control was performed and has been reported in detail previously²⁵. Genotype imputation in EA and AA participants was conducted separately using genotyped SNPs with minor allele frequency (MAF) > 0.01, call rate >0.95, and Hardy-Weinberg equilibrium P > 0.00001 using the 1000 Genomes March 2012 ALL reference haplotype panel. Pre-phasing was performed using SHAPEIT2²⁶, and subsequent imputation was carried out using IMPUTE2²⁷. The imputed genotype dosages were filtered to retain only SNPs with MAF ≥0.01 and of imputation quality ≥0.3. To account for potential population stratification, ten principal components were estimated separately for EA and AA participants using a subset of the GWAS SNPs with the software EIGENSTRAT²⁸. The first 10 principal components were included in the respective linear regression models to control for population stratification.