A Genome-Wide Association Study Identifies LIPA as a Susceptibility Gene for Coronary Artery Disease
| Autor: | Juergen Schrezenmeir, Heidi Rossmann, Joshua C. Bis, Tanja Zeller, Heinz Erich Wichmann, Sandra Wilde, Jeanette Erdmann, Serkalem Demissie, Wibke Reinhard, Roberto Elosua, Arne Schillert, Vilmundur Gudnason, Albert Hofman, Sekar Kathiresan, Philipp S. Wild, Christoph Bickel, François Cambien, Stefan Schreiber, Mary Susan Burnett, Eric Boerwinkle, Klaus Stark, Nour Eddine El Mokthari, Stefan Blankenberg, Mingyao Li, Veikko Salomaa, Medea S. Eleftheriadis, Marcus E. Kleber, Dominique Arveiler, Alun Evans, Kaisa Silander, Jarmo Virtamo, Michael M. Hoffmann, Arne Schäfer, Andreas Ziegler, Patrick Diemert, Till Keller, Aaron R. Folsom, Peter S. Braund, Annette Peters, Karl J. Lackner, Nehal N. Mehta, Stephen M. Schwartz, Nilesh J. Samani, Inke R. König, Heribert Schunkert, Renate B. Schnabel, Jens Baumert, L. Adrienne Cupples, André G. Uitterlinden, Tamara B. Harris, Muredach P. Reilly, Per-Gunnar Wiklund, Hans J. Rupprecht, Maja Barbalić, Jaqueline C M Witteman, Frank Kee, Jean Ferrières, Edith Lubos, Hendrik B. Sager, David S. Siscovick, Liming Qu, Norman Klopp, Daniel J. Rader, Thomas Münzel, Joseph M. Devaney, Hakon Hakonarson, Benjamin F. Voight, Stephen E. Epstein, Emmanuelle Yon, Albert V. Smith, Silke Szymczak, Claire Perret, Christoph Sinning, Diana Rubin, Maryam Kavousi, David Altshuler, Laurence Tiret, Carole Proust, Christopher J. O'Donnell, John R. Thompson, Winfried März, Olli Saarela, Arne Deiseroth, Thomas Illig, Philippe Amouyel, Christian Hengstenberg, Olle Melander, Kari Kuulasmaa, Alistair S. Hall |
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| Přispěvatelé: | Epidemiology, Internal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Genomics
Genome-wide association study Coronary Artery Disease 030204 cardiovascular system & hematology Biology Polymorphism Single Nucleotide Article Monocytes Coronary artery disease 03 medical and health sciences 0302 clinical medicine Genetic variation medicine Genetics coronary artery disease genome-wide association studies gene expression genetic variation genomics eQTL eSNP LIPA Humans Genetic Predisposition to Disease Genetics(clinical) RNA Messenger Gene Genetics (clinical) 030304 developmental biology Genetic association 0303 health sciences Chromosomes Human Pair 10 Gene Expression Profiling Genetic Variation Sterol Esterase medicine.disease Gene expression profiling Case-Control Studies Expression quantitative trait loci Endothelium Vascular Cardiology and Cardiovascular Medicine Genome-Wide Association Study |
| Zdroj: | Circulation: Cardiovascular Genetics Wild, P S, Zeller, T, Schillert, A, Kee, F & Evans, A 2011, ' A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease ', Circulation. Cardiovascular genetics, vol. 4, no. 4, pp. 403-412 . https://doi.org/10.1161/CIRCGENETICS.110.958728 Circulation-cardiovascular genetics, 4(4), 403-U203. Lippincott Williams & Wilkins |
| ISSN: | 1942-3268 1942-325X |
| DOI: | 10.1161/CIRCGENETICS.110.958728 |
| Popis: | Background— eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD). Methods and Results— In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucleotide polymorphisms (SNPs) that were associated with CAD at P −3 . Subsequent in silico and wet-laboratory replication stages and a final meta-analysis of 21 428 CAD cases and 38 361 control subjects revealed a novel association signal at chromosome 10q23.31 within the LIPA (lysosomal acid lipase A) gene ( P =3.7×10 −8 ; odds ratio, 1.1; 95% confidence interval, 1.07 to 1.14). The association of this locus with global gene expression was assessed by genome-wide expression analyses in the monocyte transcriptome of 1494 individuals. The results showed a strong association of this locus with expression of the LIPA transcript ( P =1.3×10 −96 ). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function ( P =4.4×10 −3 ). Conclusions— The use of data on genetic variants and the addition of data on global monocytic gene expression led to the identification of the novel functional CAD susceptibility locus LIPA , located on chromosome 10q23.31. The respective eSNPs associated with CAD strongly affect LIPA gene expression level, which was related to endothelial dysfunction, a precursor of CAD. |
| Databáze: | OpenAIRE |
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