TY - JOUR
T1 - Framingham's contribution to gene identification for CV risk factors and coronary disease
AU - Ehret, Georg B.
N1 - Funding Information:
Georg B. Ehret is co-chair of the CHARGE BP working group, of the ICBP-SC, and a member of the Family Blood Pressure Program Essential Hypertension Genome-Wide Association Studies (FEHGAS) group. Ehret's work is partly supported by grant # FN 33CM30-124087 of the Swiss National Science Foundation ; by grant # 5R01HL086694 of the National Heart, Lung, and Blood Institute (NHLBI); and by the Research and Development Budget of the Geneva University Hospital . Parts of this text are used in the “thèse de privat-docent” of the author.
PY - 2013/3
Y1 - 2013/3
N2 - Genome-wide association studies have been published since 2005 and remain exemplary in translating knowledge fostered by the human genome project into genomic lessons on health and disease. Although our understanding of the basis of complex disease remains by far incomplete, the knowledge of the genetic basis of cardiovascular risk factors and their end organ damage has been significantly improved. The Framingham Heart Study was one of the earliest population-based studies to apply genomic methods and is an important contributor to large disease-based consortia as the International Consortium for Blood Pressure Genome-Wide Association Studies, the Global Lipids Genetics Consortium, the Diabetes Genetics Replication and Meta-Analysis Consortium, and the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Consortium. The variability of these cardiovascular risk factors is partly genetic and knowledge on the genetic basis originated largely from analysis of monogenic disease in rare syndromes before the use of genome-wide, common single nucleotide polymorphism analysis. Genome-wide association studies have identified ∼45 common variants associated with systolic and diastolic blood pressure, ∼65 common variants for type 2 diabetes, and ∼95 common variants for lipid traits. One major type of end organ damage is coronary heart disease, and ∼25 loci could be shown to be associated. Risk scores using multiple cardiovascular risk factor single nucleotide polymorphisms are clearly correlated with cardiovascular outcome. This review summarizes recent findings by genome-wide association studies and the contributions by the Framingham Heart Study on the basis of seminal papers and gives an outlook on some of the future experiments.
AB - Genome-wide association studies have been published since 2005 and remain exemplary in translating knowledge fostered by the human genome project into genomic lessons on health and disease. Although our understanding of the basis of complex disease remains by far incomplete, the knowledge of the genetic basis of cardiovascular risk factors and their end organ damage has been significantly improved. The Framingham Heart Study was one of the earliest population-based studies to apply genomic methods and is an important contributor to large disease-based consortia as the International Consortium for Blood Pressure Genome-Wide Association Studies, the Global Lipids Genetics Consortium, the Diabetes Genetics Replication and Meta-Analysis Consortium, and the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Consortium. The variability of these cardiovascular risk factors is partly genetic and knowledge on the genetic basis originated largely from analysis of monogenic disease in rare syndromes before the use of genome-wide, common single nucleotide polymorphism analysis. Genome-wide association studies have identified ∼45 common variants associated with systolic and diastolic blood pressure, ∼65 common variants for type 2 diabetes, and ∼95 common variants for lipid traits. One major type of end organ damage is coronary heart disease, and ∼25 loci could be shown to be associated. Risk scores using multiple cardiovascular risk factor single nucleotide polymorphisms are clearly correlated with cardiovascular outcome. This review summarizes recent findings by genome-wide association studies and the contributions by the Framingham Heart Study on the basis of seminal papers and gives an outlook on some of the future experiments.
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U2 - 10.1016/j.gheart.2012.12.010
DO - 10.1016/j.gheart.2012.12.010
M3 - Review article
C2 - 23853761
AN - SCOPUS:84875188473
VL - 8
SP - 59
EP - 65
JO - CVD Prevention and Control
JF - CVD Prevention and Control
SN - 2211-8160
IS - 1
ER -