| Title : A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease - Wild_2011_Circ.Cardiovasc.Genet_4_403 |
| Author(s) : Wild PS , Zeller T , Schillert A , Szymczak S , Sinning CR , Deiseroth A , Schnabel RB , Lubos E , Keller T , Eleftheriadis MS , Bickel C , Rupprecht HJ , Wilde S , Rossmann H , Diemert P , Cupples LA , Perret C , Erdmann J , Stark K , Kleber ME , Epstein SE , Voight BF , Kuulasmaa K , Li M , Schafer AS , Klopp N , Braund PS , Sager HB , Demissie S , Proust C , Konig IR , Wichmann HE , Reinhard W , Hoffmann MM , Virtamo J , Burnett MS , Siscovick D , Wiklund PG , Qu L , El Mokthari NE , Thompson JR , Peters A , Smith AV , Yon E , Baumert J , Hengstenberg C , Marz W , Amouyel P , Devaney J , Schwartz SM , Saarela O , Mehta NN , Rubin D , Silander K , Hall AS , Ferrieres J , Harris TB , Melander O , Kee F , Hakonarson H , Schrezenmeir J , Gudnason V , Elosua R , Arveiler D , Evans A , Rader DJ , Illig T , Schreiber S , Bis JC , Altshuler D , Kavousi M , Witteman JC , Uitterlinden AG , Hofman A , Folsom AR , Barbalic M , Boerwinkle E , Kathiresan S , Reilly MP , O'Donnell CJ , Samani NJ , Schunkert H , Cambien F , Lackner KJ , Tiret L , Salomaa V , Munzel T , Ziegler A , Blankenberg S |
| Ref : Circ Cardiovasc Genet , 4 :403 , 2011 |
|
Abstract :
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<10(-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=3.7x10(-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=1.3x10(-96)). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function (P=4.4x10(-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. |
| PubMedSearch : Wild_2011_Circ.Cardiovasc.Genet_4_403 |
| PubMedID: 21606135 |
| Gene_locus related to this paper: human-LIPA |
| Gene_locus | human-LIPA |
Wild PS, Zeller T, Schillert A, Szymczak S, Sinning CR, Deiseroth A, Schnabel RB, Lubos E, Keller T, Eleftheriadis MS, Bickel C, Rupprecht HJ, Wilde S, Rossmann H, Diemert P, Cupples LA, Perret C, Erdmann J, Stark K, Kleber ME, Epstein SE, Voight BF, Kuulasmaa K, Li M, Schafer AS, Klopp N, Braund PS, Sager HB, Demissie S, Proust C, Konig IR, Wichmann HE, Reinhard W, Hoffmann MM, Virtamo J, Burnett MS, Siscovick D, Wiklund PG, Qu L, El Mokthari NE, Thompson JR, Peters A, Smith AV, Yon E, Baumert J, Hengstenberg C, Marz W, Amouyel P, Devaney J, Schwartz SM, Saarela O, Mehta NN, Rubin D, Silander K, Hall AS, Ferrieres J, Harris TB, Melander O, Kee F, Hakonarson H, Schrezenmeir J, Gudnason V, Elosua R, Arveiler D, Evans A, Rader DJ, Illig T, Schreiber S, Bis JC, Altshuler D, Kavousi M, Witteman JC, Uitterlinden AG, Hofman A, Folsom AR, Barbalic M, Boerwinkle E, Kathiresan S, Reilly MP, O'Donnell CJ, Samani NJ, Schunkert H, Cambien F, Lackner KJ, Tiret L, Salomaa V, Munzel T, Ziegler A, Blankenberg S (2011)
A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease
Circ Cardiovasc Genet
4 :403
Wild PS, Zeller T, Schillert A, Szymczak S, Sinning CR, Deiseroth A, Schnabel RB, Lubos E, Keller T, Eleftheriadis MS, Bickel C, Rupprecht HJ, Wilde S, Rossmann H, Diemert P, Cupples LA, Perret C, Erdmann J, Stark K, Kleber ME, Epstein SE, Voight BF, Kuulasmaa K, Li M, Schafer AS, Klopp N, Braund PS, Sager HB, Demissie S, Proust C, Konig IR, Wichmann HE, Reinhard W, Hoffmann MM, Virtamo J, Burnett MS, Siscovick D, Wiklund PG, Qu L, El Mokthari NE, Thompson JR, Peters A, Smith AV, Yon E, Baumert J, Hengstenberg C, Marz W, Amouyel P, Devaney J, Schwartz SM, Saarela O, Mehta NN, Rubin D, Silander K, Hall AS, Ferrieres J, Harris TB, Melander O, Kee F, Hakonarson H, Schrezenmeir J, Gudnason V, Elosua R, Arveiler D, Evans A, Rader DJ, Illig T, Schreiber S, Bis JC, Altshuler D, Kavousi M, Witteman JC, Uitterlinden AG, Hofman A, Folsom AR, Barbalic M, Boerwinkle E, Kathiresan S, Reilly MP, O'Donnell CJ, Samani NJ, Schunkert H, Cambien F, Lackner KJ, Tiret L, Salomaa V, Munzel T, Ziegler A, Blankenberg S (2011)
Circ Cardiovasc Genet
4 :403