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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Large scale association analysis of novel genetic loci for coronary artery disease.
Arterioscler. Thromb. Vasc. Biol. 29, 774-780 (2009)
Background-Combined analysis of 2 genome-wide association studies in cases enriched for family history recently identified 7 loci (on 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21, 10q11.21, and 15q22.33) that may affect risk of coronary artery disease (CAD). Apart from the 9p21 locus, the other loci await substantive replication. Furthermore, the effect of these loci on CAD risk in a broader range of individuals remains to be determined. Methods and Results-We undertook association analysis of single nucleotide polymorphisms at each locus with CAD risk in 11 550 cases and 11 205 controls from 9 European studies. The 9p21.3 locus showed unequivocal association (rs1333049, combined odds ratio [OR]=1.20, 95% CI [1.16 to 1.25], probability value=2.81x10(-21)). We also confirmed association signals at 1p13.3 (rs599839, OR=1.13 [1.08 to 1.19], P=1.44x10(-7)), 1q41 (rs3008621, OR=1.10 [1.04 to 1.17], P=1.02x10(-3)), and 10q11.21 (rs501120, OR=1.11 [1.05 to 1.18], P=4.34x10(-4)). The associations with 6q25.1 (rs6922269, P=0.020) and 2q36.3 (rs2943634, P=0.032) were borderline and not statistically significant after correction for multiple testing. The 15q22.33 locus did not replicate. The 10q11.21 locus showed a possible sex interaction (P = 0.015), with a significant effect in women (OR=1.29 [1.15 to 1.45], P=1.86x10(-5)) but not men (OR=1.03 [0.96 to 1.11], P=0.387). There were no other strong interactions of any of the loci with other traditional risk factors. The loci at 9p21, 1p13.3, 2q36.3, and 10q11.21 acted independently and cumulatively increased CAD risk by 15% (12% to 18%), per additional risk allele. ConclusionsThe findings provide strong evidence for association between at least 4 genetic loci and CAD risk. Cumulatively, these novel loci have a significant impact on risk of CAD at least in European populations.
Impact Factor
Scopus SNIP
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Times Cited
Times Cited
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6.858
2.350
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Anmerkungen
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
coronary artery disease; genetics; risk factors; genome-wide association; myocardial-infarction; heart-disease; european-society; working group; risk; cholesterol; population; susceptibility; metaanalysis
Sprache
englisch
Veröffentlichungsjahr
2009
HGF-Berichtsjahr
0
ISSN (print) / ISBN
1079-5642
e-ISSN
1524-4636
Quellenangaben
Band: 29,
Heft: 5,
Seiten: 774-780
Verlag
Lippincott Williams & Wilkins
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epidemiology (EPI)
PSP-Element(e)
G-503900-004
PubMed ID
19164808
Erfassungsdatum
2009-07-09