Fine mapping of a linkage peak with integration of lipid traits identifies novel coronary artery disease genes on chromosome 5

We identified four genes with SNPs that showed the strongest and most consistent associations with LDL-C and CAD: EBF1, PPP2R2B, SPOCK1, and PRELID2. The most significant results for association of SNPs with LDL-C were: EBF1, rs6865969, p = 0.01; PPP2R2B, rs2125443, p = 0.005; SPOCK1, rs17600115, p = 0.003; and PRELID2, rs10074645, p = 0.0002). The most significant results for CAD were EBF1, rs6865969, p = 0.007; PPP2R2B, rs7736604, p = 0.0003; SPOCK1, rs17170899, p = 0.004; and PRELID2, rs7713855, p = 0.003.Using an intermediate disease-related quantitative trait of LDL-C we have identified four novel CAD genes, EBF1, PRELID2, SPOCK1, and PPP2R2B. These four genes should be further examined in future functional studies as candidate susceptibility loci for cardiovascular disease mediated through LDL-cholesterol pathways.Coronary artery disease (CAD) is the end result of accumulation of atheromatous plaques in the coronary arteries, leading to eventual impairment of cardiac blood flow and potentially devastating consequences of myocardial infarction (MI) or death. CAD is the leading cause of death in both the United States and worldwide, with over 500,000 deaths per year in the U.S. and over seven million worldwide (World Health Organization) [1]. Despite the development of pharmacologic therapies for prevention, the incidence of CAD is increasing, concomitant with the rising prevalence of risk factors such as obesity and diabetes (American Heart Association) [2].CAD itself is clearly a heritable trait, with the role of genetic factors becoming increasingly apparent in early-onset CAD [3-5]. However, the genetic architecture of CAD, as with many common diseases, is assumed to be complex and continues to be poorly understood. Candidate gene studies have identified several loci for CAD, but with inconsistent results in validation cohorts. Recent genome wide association studies (GWAS) have consistently identified a locus on chromosome 9p21; however, this locus confers o