Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population: the Suita study.
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.


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.
Hiura
Yumiko
Y
Department of Epidemiology, Research Institute, National Cardiovascular Center, Suita 565-8565, Japan.
Shen
Chun-Shen
CS
Kokubo
Yoshihiro
Y
Okamura
Tomonori
T
Morisaki
Takayuki
T
Tomoike
Hitonobu
H
Yoshida
Teruhiko
T
Sakamoto
Hiromi
H
Goto
Yoichi
Y
Nonogi
Hiroshi
H
Iwai
Naoharu
N
D000328:Adult; D000368:Aged; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D016022:Case-Control Studies; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL