Erdmann, Jeanette and Willenborg, Christina and Nahrstaedt, Janja and Preuss, Michael and Koenig, Inke R. and Baumert, Jens and Linsel-Nitschke, Patrick and Gieger, Christian and Tennstedt, Stephanie and Belcredi, Petra and Aherrahrou, Zouhair and Klopp, Norman and Loley, Christina and Stark, Klaus and Hengstenberg, Christian and Bruse, Petra and Freyer, Jennifer and Wagner, Arnika K. and Medack, Anja and Lieb, Wolfgang and Grosshennig, Anika and Sager, Hendrik B. and Reinhardt, Adrian and Schaefer, Arne and Schreiber, Stefan and El Mokhtari, Nour Eddine and Raaz-Schrauder, Dorette and Illig, Thomas and Garlichs, Christoph D. and Ekici, Arif B. and Reis, Andre and Schrezenmeir, Juergen and Rubin, Diana and Ziegler, Andreas and Wichmann, H. -E. and Doering, Angela and Meisinger, Christa and Meitinger, Thomas and Peters, Annette and Schunkert, Heribert (2011) Genome-wide association study identifies a new locus for coronary artery disease on chromosome 10p11.23. EUROPEAN HEART JOURNAL, 32 (2). pp. 158-168. ISSN 0195-668X,
Full text not available from this repository. (Request a copy)Abstract
Aims Recent genome-wide association (GWA) studies identified 10 chromosomal loci for coronary artery disease (CAD) or myocardial infarction (MI). However, these loci explain only a small proportion of the genetic variability of these pertinent diseases. We sought to identify additional CAD/MI loci by applying a three-stage approach. Methods and results We genotyped n = 1157 MI cases and n = 1748 controls from a population-based study population [German MI Family Study (GerMIFS) III (KORA)] with genome-wide SNP arrays. At this first stage, n = 462 SNPs showed association with MI at P < 1 x 10(-3) in two-sided logistic regression. In a second stage, 415 of these SNPs were evaluated in silico in two independent GWA samples, the GerMIFS I (875 cases/1644 controls) and GerMIFS II (1222 cases/1298 controls). Nine SNPs, representing three regions, displayed consistent replication in this in silico analysis (P < 0.05 for each GWA sample): five SNPs at 9p21.3, a well-known CAD/MI locus, two SNPs at 10p11.21, and two SNPs at 2p24.3. Wet-lab replication, i.e. the third stage, of SNP rs3739998 (representing the novel locus at 10p11.21, p. S1002T in the KIAA1462 gene) in additional 5790 cases and 5302 controls confirmed the association (P = 9.54 x 10(-4)), but not for the 2p24.3 locus. The combined P-value across all stages for SNP rs3739998 is P = 1.27 x 10(-11) [ odds ratio (OR) = 1.15 (1.11-1.20)]. Conclusion Analysis of a GWA study followed by in silico and wet-lab replication steps identified the KIAA1462 gene, encoding a yet uncharacterized protein, on chromosome 10p11.23 with genome-wide significant association for CAD/MI. Further studies are needed to characterize the functional role of this locus in the aetiology of these diseases.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MYOCARDIAL-INFARCTION; GENETIC ASSOCIATION; GENOTYPE; AUGSBURG; RISK; SUSCEPTIBILITY; POLYMORPHISMS; REPLICATION; ONSET; MEN; Genome-wide association study; GWA; Myocardial infarction; Coronary artery disease; Genetics; KIAA1462; Chromosome 9p21.3 |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jun 2020 12:05 |
| Last Modified: | 29 Jun 2020 12:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21570 |
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