TY - JOUR
T1 - Genetic architecture of coronary artery disease in the genome-wide era
T2 - implications for the emerging "golden dozen" loci.
AU - Girelli, Domenico
AU - Martinelli, Nicola
AU - Peyvandi, Flora
AU - Olivieri, Oliviero
PY - 2009/10
Y1 - 2009/10
N2 - Clinicians are well aware of family history as a risk factor for coronary artery disease (CAD) and myocardial infarction (MI). The underlying genetic architecture of CAD/MI is extremely complex and still poorly understood. Overall, the genetic heritability of CAD/MI is estimated to be near 40 to 60%. This proportion includes mainly genes that regulate known risk factors (e.g., lipid metabolism) but also genes involved in as yet unknown metabolic pathways. In the last 2 years, the systematic application of genome-wide association studies in the setting of large collaborative consortia including thousands of patients and controls has led to the identification of several new loci associated with CAD/MI. Here we review current knowledge on the emerging "top" 12 loci, that is, those showing the most consistent associations with clinical phenotypes. Although these genetic variants have little or no current predictive value of at the level of individual patients, they have the potential to disclose novel biological mechanisms involved in the pathophysiology of CAD/MI. (c) Thieme Medical Publishers.
AB - Clinicians are well aware of family history as a risk factor for coronary artery disease (CAD) and myocardial infarction (MI). The underlying genetic architecture of CAD/MI is extremely complex and still poorly understood. Overall, the genetic heritability of CAD/MI is estimated to be near 40 to 60%. This proportion includes mainly genes that regulate known risk factors (e.g., lipid metabolism) but also genes involved in as yet unknown metabolic pathways. In the last 2 years, the systematic application of genome-wide association studies in the setting of large collaborative consortia including thousands of patients and controls has led to the identification of several new loci associated with CAD/MI. Here we review current knowledge on the emerging "top" 12 loci, that is, those showing the most consistent associations with clinical phenotypes. Although these genetic variants have little or no current predictive value of at the level of individual patients, they have the potential to disclose novel biological mechanisms involved in the pathophysiology of CAD/MI. (c) Thieme Medical Publishers.
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M3 - Article
C2 - 20013534
AN - SCOPUS:77449107943
VL - 35
SP - 671
EP - 682
JO - Seminars in Thrombosis and Hemostasis
JF - Seminars in Thrombosis and Hemostasis
SN - 0094-6176
IS - 7
ER -