Background: Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels. Given the difference in allele frequencies and linkage disequilibrium patterns across the populations, a GWAS was conducted using the Illumina 550K in a Japanese population (n=900) in search of population-specific genetic variations associated with high-density lipoprotein (HDL)-cholesterol.
Methods and results: Among the 368,274 single nucleotide polymorphisms (SNPs) with a minor allele frequency of at least 0.1, 43 SNPs exceeded the arbitrary threshold of -log(10)P >4.0. The most significant SNP was rs3764261, located 5'upstream of CETP, exhibiting a -log(10)P value of 6.17. Increasing the sample size by genotyping in the additional Suita sample (n=1,810) further improved the level of significance, with each additional copy of the minor allele being associated with an increase in HDL-cholesterol by 6.2 mg/dl (P =3.4x10(-12)). Interestingly, the minor allele was more prevalent in cases with myocardial infarction than in controls (0.221 vs 0.196, nominal P=0.02).
Conclusions: The association between genetic variants at CETP and HDL-cholesterol was replicated in our sample. None of the genetic variants exerted a greater influence on HDL levels than those at CETP. Associations for the top-ranked SNPs need to be tested for further replication in an independent sample.