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

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1119-1126
Number of pages8
JournalCirculation Journal
Volume73
Issue number6
DOIs
Publication statusPublished - 2009 Jun
Externally publishedYes

Fingerprint

Genetic Markers
HDL Cholesterol
Single Nucleotide Polymorphism
Genome
Genome-Wide Association Study
Gene Frequency
Population
Alleles
Linkage Disequilibrium
Population Genetics
HDL Lipoproteins
Sample Size
Myocardial Infarction
Lipids
Genes

Keywords

  • Genetics
  • HDL-cholesterol
  • Single nucleotide polymorphism

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population - The Suita study. / Hiura, Yumiko; Shen, Chun Shen; Kokubo, Yoshihiro; Okamura, Tomonori; Morisaki, Takayuki; Tomoike, Hitonobu; Yoshida, Teruhiko; Sakamoto, Hiromi; Goto, Yoichi; Nonogi, Hiroshi; Iwai, Naoharu.

In: Circulation Journal, Vol. 73, No. 6, 06.2009, p. 1119-1126.

Research output: Contribution to journalArticle

Hiura, Y, Shen, CS, 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, vol. 73, no. 6, pp. 1119-1126. https://doi.org/10.1253/circj.CJ-08-1101
Hiura, Yumiko ; Shen, Chun Shen ; Kokubo, Yoshihiro ; Okamura, Tomonori ; Morisaki, Takayuki ; Tomoike, Hitonobu ; Yoshida, Teruhiko ; Sakamoto, Hiromi ; Goto, Yoichi ; Nonogi, Hiroshi ; Iwai, Naoharu. / Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population - The Suita study. In: Circulation Journal. 2009 ; Vol. 73, No. 6. pp. 1119-1126.
@article{9b3ff9b2b775474d8fba9011d97499d7,
title = "Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population - The Suita study",
abstract = "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.",
keywords = "Genetics, HDL-cholesterol, Single nucleotide polymorphism",
author = "Yumiko Hiura and Shen, {Chun Shen} and Yoshihiro Kokubo and Tomonori Okamura and Takayuki Morisaki and Hitonobu Tomoike and Teruhiko Yoshida and Hiromi Sakamoto and Yoichi Goto and Hiroshi Nonogi and Naoharu Iwai",
year = "2009",
month = "6",
doi = "10.1253/circj.CJ-08-1101",
language = "English",
volume = "73",
pages = "1119--1126",
journal = "Circulation Journal",
issn = "1346-9843",
publisher = "Japanese Circulation Society",
number = "6",

}

TY - JOUR

T1 - Identification of genetic markers associated with high-density lipoprotein-cholesterol by genome-wide screening in a Japanese population - The Suita study

AU - Hiura, Yumiko

AU - Shen, Chun Shen

AU - Kokubo, Yoshihiro

AU - Okamura, Tomonori

AU - Morisaki, Takayuki

AU - Tomoike, Hitonobu

AU - Yoshida, Teruhiko

AU - Sakamoto, Hiromi

AU - Goto, Yoichi

AU - Nonogi, Hiroshi

AU - Iwai, Naoharu

PY - 2009/6

Y1 - 2009/6

N2 - 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.

AB - 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.

KW - Genetics

KW - HDL-cholesterol

KW - Single nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=67649875301&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649875301&partnerID=8YFLogxK

U2 - 10.1253/circj.CJ-08-1101

DO - 10.1253/circj.CJ-08-1101

M3 - Article

VL - 73

SP - 1119

EP - 1126

JO - Circulation Journal

JF - Circulation Journal

SN - 1346-9843

IS - 6

ER -