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Open Access Green as soon as Postprint is submitted to ZB.
Genome-wide association analysis of high-density lipoprotein cholesterol in the population-based KORA study sheds new light on intergenic regions.
Circ. Cardiovasc. Genet. 1, 10-20 (2008)
Background— High-density lipoprotein cholesterol (HDLC) is a strong risk factor for atherosclerosis and is assumed to be under considerable genetic control. We aimed to identify gene regions that influence HDLC levels by a genome-wide association analysis in the population-based KORA (Cooperative Health Research in the Region of Augsburg) study. Methods and Results— In KORA S3/F3 (n=1643), we analyzed 377 865 quality-checked single-nucleotide polymorphisms (SNPs; 500K, Affymetrix, Santa Clara, Calif), complemented by the publicly available genome-wide association results from the Diabetes Genetics Initiative (n=2631) and by replication data from KORA S4 (n=4037) and the Copenhagen City Heart Study (n=9205). Among the 13 SNPs selected from the KORA S3/F3 500K probability value list, 3 showed consistent associations in subsequent replications: 1 SNP 10 kb upstream of CETP (pooled probability value=8.5x10–27), 1 SNP approximately 40 kb downstream of LIPG (probability value=4.67x10–10), both independent of previously reported SNPs, and 1 from an already reported region of LPL (probability value=2.82x10–11). Bioinformatical analyses indicate a potential functional relevance of the respective SNPs. Conclusions— The present genome-wide association study identified 2 interesting HDLC-relevant regions upstream of CETP and downstream of LIPG. This draws attention to the importance of long-range effects of intergenic regions, which have been underestimated so far, and may impact future candidate-gene–association studies toward extending the region analyzed. Furthermore, the present study reinforced CETP and LPL as HDLC genes and thereby underscores the power of this type of genome-wide association approach to pinpoint associations of common polymorphisms with effects explaining as little as 0.5% of the HDLC variance in the general population.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
genome; cholesterol; genetics; polymorphism; single nucleotide; genotype; genome-wide association study
ISSN (print) / ISBN
1942-325X
e-ISSN
1942-3268
Quellenangaben
Volume: 1,
Pages: 10-20
Publisher
Lippincott Williams & Wilkins
Publishing Place
Hagerstown, Md
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Epidemiology (EPI)