However, we fully recognize that extensive further studies of each of these individual putative Klf4 and Oct4 target genes will be needed to show that they have a causal role in regulating SMC phenotype and CAD pathogenesis, including determining if CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9–induced human GWAS risk alleles are associated with functional changes in SMCs that exacerbate lesion pathogenesis.47 This evidence concerns the gene KLF4 and coronary artery disorder.