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 language | English |
|---|---|
| Pages (from-to) | 1119-1126 |
| Number of pages | 8 |
| Journal | Circulation Journal |
| Volume | 73 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2009 Jun |
| Externally published | Yes |
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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 journal › Article
}
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 -