> Details

Heid, Iris M.; Boes, Eva; Müller, Martina; Kollerits, Barbara; Lamina, Claudia; Coassin, Stefan; Gieger, Christian; Döring, Angela; Klopp, Norman; Frikke-Schmidt, Ruth; Tybj�rg-Hansen, Anne; Brandstätter, Anita; Luchner, Andreas; Meitinger, Thomas; Wichmann, H.-Erich; Kronenberg, Florian

Genome-Wide Association Analysis of High-Density Lipoprotein Cholesterol in the Population-Based KORA Study Sheds New Light on Intergenic Regions

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: Genome-Wide Association Analysis of High-Density Lipoprotein Cholesterol in the Population-Based KORA Study Sheds New Light on Intergenic Regions
  • Contributor: Heid, Iris M.; Boes, Eva; Müller, Martina; Kollerits, Barbara; Lamina, Claudia; Coassin, Stefan; Gieger, Christian; Döring, Angela; Klopp, Norman; Frikke-Schmidt, Ruth; Tybj�rg-Hansen, Anne; Brandstätter, Anita; Luchner, Andreas; Meitinger, Thomas; Wichmann, H.-Erich; Kronenberg, Florian
  • imprint: Ovid Technologies (Wolters Kluwer Health), 2008
  • Published in: Circulation: Cardiovascular Genetics
  • Language: English
  • DOI: 10.1161/circgenetics.108.776708
  • ISSN: 1942-3268; 1942-325X
  • Keywords: Genetics (clinical) ; Cardiology and Cardiovascular Medicine ; Genetics
  • Origination:
  • Footnote:
  • Description: <jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> 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. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> 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 <jats:italic>CETP</jats:italic> (pooled probability value=8.5�10 <jats:sup>−27</jats:sup> ), 1 SNP approximately 40 kb downstream of <jats:italic>LIPG</jats:italic> (probability value=4.67�10 <jats:sup>−10</jats:sup> ), both independent of previously reported SNPs, and 1 from an already reported region of <jats:italic>LPL</jats:italic> (probability value=2.82�10 <jats:sup>−11</jats:sup> ). Bioinformatical analyses indicate a potential functional relevance of the respective SNPs. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> The present genome-wide association study identified 2 interesting HDLC-relevant regions upstream of <jats:italic>CETP</jats:italic> and downstream of <jats:italic>LIPG</jats:italic> . 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 <jats:italic>CETP</jats:italic> and <jats:italic>LPL</jats:italic> 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. </jats:p>
  • Access State: Open Access