• Queen Mary University of London
  • Barts Health NHS
  • Bradford NHS
  • Manchester Uni

S00013: Genotype-first recall to study extreme genetic risk of atherosclerotic cardiovascular disease

Lay summary:   Genotype-first recall to study extreme genetic risk of atherosclerotic cardiovascular disease

Please provide information on the aims of the proposed research including the research question(s) that you are aiming to answer and the health condition(s) under investigation

Cardiovascular disease is the leading cause of death in the UK. South Asians living in the UK have the highest rates of early age onset cardiovascular disease of any ethnic group. For example, in men aged 35-54 in England rates of coronary heart disease were 8% in Pakistani ethnicity individuals, 6% in Bangladeshi versus 2% in the general population. The overall aim of our proposed research is to study individuals at extremely high inherited (genetic) risk of cardiovascular disease.

The main disease we will study is coronary heart disease: blocked heart arteries causing angina and heart attack. We will also study other diseases of blocked arteries: peripheral vascular disease, stroke and vascular dementia. We will perform this research in an understudied minority ethnic group (British south Asians) already at high risk. We will use a long term population research study, Genes & Health, where volunteers have contributed genetic data, NHS health record data, and may be recalled at a future date for further research.

We will recall selected volunteers for research investigations including imaging of the heart and other arteries. Whilst cardiovascular disease is clearly a complex combination of factors such as diet, lack of exercise, obesity and smoking as well as multiple inherited genetic factors, in some individuals genetic risk is the main cause.

We will study a condition called familial hypercholesterolemia, where the levels of bad heart disease causing cholesterol in the blood are high from childhood due to a single inherited genetic change.

We will also study individuals who inherit a really bad selection of thousands of genetic variants, each of small effect but large when added together, called polygenic risk.

Neither of these genetic causes is well researched (or well treated) in south Asians. We will recall individuals based solely on their genetics, not on any other clinical features or risk factors. Most people do not know that they are at very high genetic risk of cardiovascular disease (from either familial hypercholesterolemia or polygenic risk). A family history of disease provides some information but is pretty inaccurate. In Genes & Health we will have genetic data on 100,000 volunteers and be able to provide much more accurate information.

We will first assess the rates of KNOWN cardiovascular disease in British south Asian volunteers with either genetic familial hypercholesterolemia or high polygenic risk versus those without, using NHS health records.

Next, we will recall volunteers for clinical investigations to assess the rates of UNKNOWN cardiovascular disease. We will recall all individuals with genetic familial hypercholesterolemia, and compare them to a matched group of people with average, and with very high polygenic risk.

Then, we will assess what people thought about being given their genetic results - eg. did they want this information, or did this cause anxiety?

Finally, we will treat individuals we find to be at very high risk at Barts Heart Centre (an NHS hospital) to prevent future heart attacks. There are some lifestyle ways to do this (eg. exercise more, eat better, stop smoking) and there are some very effective and pretty safe medicines (eg. statins). Relatives of high risk individuals may also be at high risk themselves, and can also benefit from prevention. We will assess how well these offers of prevention are taken up by people.

Our findings in people with very high genetic risk of cardiovascular disease will be important for other big research studies, and for larger scale population prevention including the increasing use of genetics in medicine across the NHS and worldwide.


Prof David van Heel, Dr Fizzah Choudry, Dr Riyaz Patel, Dr Sarah Finer, Professor Panos Deloukas, Dr Saskia Sanderson