Genetics of CAD

We have one of the foremost groups undertaking cardiovascular genetics research in the UK and internationally. Three major projects all funded through programme grants underpin this research: The BHF Family Heart Study, The British Genetics of Hypertension (BRIGHT) Study and The Genetic Regulation of Arterial Pressure of Humans in the Community (GRAPHIC) Study.

Linkage disequilibrium graph

Using these and other resources we have contributed to internationally leading research in the field of cardiovascular genetics. Perhaps most notable is the involvement of both the BHF Family Heart Study and the BRIGHT study in the ground-breaking Wellcome Trust Case Control Consortium (WTCCC) project, which investigated the genetic basis of seven common diseases using a genome-wide association approach, reporting in 2007 (Nature 2007; 447:661–678). Professor Nilesh Samani is a member of the WTCCC Management Committee and PI for the CAD component. Ongoing work has included looking at the role of copy number variants, concluding that these do not contribute to the risk of common diseases including coronary artery disease and do not explain a significant proportion of the missing heritability of these diseases (Nature 2010; 464:713-20). In other international collaborative studies, we identified 8 new loci that affect blood pressure and risk of hypertension that contain genes which have hitherto not been implicated in blood pressure regulation and thus provide novel targets for future treatments (Nat Genet 2009; 41: 666-676.). More recently, as part of the CARDIoGRAM consortium (co-led by Professor Nilesh Samani), we identified 13 new loci for coronary artery disease (Nat Genet 2011; 43:333-338). Our work in this field was further recognised by the award of a European Union FP6 Integrated Project, Cardiogenics (2006-2010) which took the genome-wide association signals forward into functional and translational studies. Other highlights include identification of the first human genetic variant that associates with telomere length, a marker of biological ageing (Nat Genet 2010; 42: 197-9). The findings could have important implications for our understanding of common age-associated diseases such as heart disease and cancer.

Immunohistochemistry showing FGF binding protein in the glomerulusThe clinical studies are complemented by studies in experimental models through a Wellcome Trust Cardiovascular Functional Genomics Programme Grant (2003-2009). Specifically, we have mapped and extensively investigated a major quantitative trait locus regulating blood pressure (BP) on rat chromosome 1 using a range of approaches including gene knock-out, renal transplantation and microarray expression profiling.

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