Genome-Wide Association Study Pinpoints a New Functional Apolipoprotein B Variant Influencing Oxidized Low-Density Lipoprotein Levels But Not Cardiovascular Events

Background—Oxidized low-density lipoprotein may be a key factor in the development of atherosclerosis. We performed a genome-wide association study on oxidized low-density lipoprotein and tested the impact of associated single-nucleotide polymorphisms (SNPs) on the risk factors of atherosclerosis and cardiovascular events. Methods and Results—A discovery genome-wide association study was performed on a population of young healthy white individuals (N=2080), and the SNPs associated with a P<5×10–8 were replicated in 2 independent samples (A: N=2912; B: N=1326). Associations with cardiovascular endpoints were also assessed with 2 additional clinical cohorts (C: N=1118; and D: N=808). We found 328 SNPs associated with oxidized low-density lipoprotein. The genetic variant rs676210 (Pro2739Leu) in apolipoprotein B was the proxy SNP behind all associations (P=4.3×10–136, effect size=13.2 U/L per allele). This association was replicated in the 2 independent samples (A and B, P=2.5×10–47 and 1.1×10–11, effect siz...