Gene filtering schema. Variants were filtered by focusing on coding and noncoding functional modifying changes. Rare variants are defined as variants with a minor allele frequency less than 1% in European American or African American populations based on data from the Exome Variant Server database (National Heart, Lung, and Blood Institute Exome Sequencing Project). Predicted pathogenic mutations are rare nonsense mutations, indels, or missense variants with highly positive pathogenicity predications using SIFT, PolyPhen-2, MutationTaster, and Align GVGD. SNP, single nucleotide polymorphism; UTR, untranslated region; VUCS, variant with uncertain clinical significance.