- Comment in:
-
Circ J. 2009 Jun;73(6):1016-7.
Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population: the Suita study.
Hiura Y,
Shen CS,
Kokubo Y,
Okamura T,
Morisaki T,
Tomoike H,
Yoshida T,
Sakamoto H,
Goto Y,
Nonogi H,
Iwai N.
Department of Epidemiology, Research Institute, National Cardiovascular Center, Suita 565-8565, Japan.
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.
PMID: 19359809 [PubMed - in process]