Heid, Iris M. and Boes, Eva and Mueller, Martina and Kollerits, Barbara and Lamina, Claudia and Coassin, Stefan and Gieger, Christian and Doering, Angela and Klopp, Norman and Frikke-Schmidt, Ruth and Tybjaerg-Hansen, Anne and Brandstaetter, Anita and Luchner, Andreas and Meitinger, Thomas and Wichmann, H. -Erich and Kronenberg, Florian (2008) Genome-Wide Association Analysis of High-Density Lipoprotein Cholesterol in the Population-Based KORA Study Sheds New Light on Intergenic Regions. CIRCULATION-CARDIOVASCULAR GENETICS, 1 (1). 10-U65. ISSN 1942-325X, 1942-3268
Full text not available from this repository. (Request a copy)Abstract
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. (Circ Cardiovasc Genet. 2008;1:10-20.)
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; genome; cholesterol; genetics; polymorphism, single nucleotide; genotype; genome-wide association study |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Oct 2020 08:36 |
| Last Modified: | 22 Oct 2020 08:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30201 |
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