Thus, in this two-stage case-control study, we assessed the associations of SNP rs2107595 with CAD risk and the severity of coronary atherosclerosis, and further performed a genotype-phenotype analysis by detecting HDAC9 mRNA expression and plasma HDAC9 levels, followed by subgroup and multifactor dimensionality reduction (MDR) analyses to explore the potential gene-environment interactions. Here, HDAC9 is linked to coronary atherosclerosis.