TY - JOUR
T1 - Genome-wide association study identifies a new locus for coronary artery disease on chromosome 10p11.23
AU - Erdmann, Jeanette
AU - Willenborg, Christina
AU - Nahrstaedt, Janja
AU - Preuss, Michael
AU - König, Inke R.
AU - Baumert, Jens
AU - Linsel-Nitschke, Patrick
AU - Gieger, Christian
AU - Tennstedt, Stephanie
AU - Belcredi, Petra
AU - Aherrahrou, Zouhair
AU - Klopp, Norman
AU - Loley, Christina
AU - Stark, Klaus
AU - Hengstenberg, Christian
AU - Bruse, Petra
AU - Freyer, Jennifer
AU - Wagner, Arnika K.
AU - Medack, Anja
AU - Lieb, Wolfgang
AU - Großhennig, Anika
AU - Sager, Hendrik B.
AU - Reinhardt, Adrian
AU - Schäfer, Arne
AU - Schreiber, Stefan
AU - El Mokhtari, Nour Eddine
AU - Raaz-Schrauder, Dorette
AU - Illig, Thomas
AU - Garlichs, Christoph D.
AU - Ekici, Arif B.
AU - Reis, André
AU - Schrezenmeir, Jrgen
AU - Rubin, Diana
AU - Ziegler, Andreas
AU - Wichmann, H. E.
AU - Doering, Angela
AU - Meisinger, Christa
AU - Meitinger, Thomas
AU - Peters, Annette
AU - Schunkert, Heribert
PY - 2011/1/1
Y1 - 2011/1/1
N2 - AimsRecent 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 resultsWe 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 × 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 (P9.54 × 10 -4), but not for the 2p24.3 locus. The combined P-value across all stages for SNP rs3739998 is P1.27 × 10 -11 [odds ratio (OR) 1.15 (1.111.20)].ConclusionAnalysis 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.
AB - AimsRecent 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 resultsWe 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 × 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 (P9.54 × 10 -4), but not for the 2p24.3 locus. The combined P-value across all stages for SNP rs3739998 is P1.27 × 10 -11 [odds ratio (OR) 1.15 (1.111.20)].ConclusionAnalysis 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.
UR - http://www.scopus.com/inward/record.url?scp=78651492334&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehq405
DO - 10.1093/eurheartj/ehq405
M3 - Journal articles
C2 - 21088011
AN - SCOPUS:78651492334
SN - 0195-668X
VL - 32
SP - 158
EP - 168
JO - European Heart Journal
JF - European Heart Journal
IS - 2
ER -
