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

Yumiko Hiura, Chun Shen Shen, Yoshihiro Kokubo, Tomonori Okamura, Takayuki Morisaki, Hitonobu Tomoike, Teruhiko Yoshida, Hiromi Sakamoto, Yoichi Goto, Hiroshi Nonogi, Naoharu Iwai

研究成果: Article

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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 -log10P >4.0. The most significant SNP was rs3764261, located 5′upstream of CETP, exhibiting a -log10P 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=3.4×10-12). 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.

元の言語English
ページ(範囲)1119-1126
ページ数8
ジャーナルCirculation Journal
73
発行部数6
DOI
出版物ステータスPublished - 2009 6 1
外部発表Yes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Hiura, Y., Shen, C. S., Kokubo, Y., Okamura, T., Morisaki, T., Tomoike, H., Yoshida, T., Sakamoto, H., Goto, Y., Nonogi, H., & Iwai, N. (2009). Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population - The Suita study. Circulation Journal, 73(6), 1119-1126. https://doi.org/10.1253/circj.CJ-08-1101