S000011: The genetic architecture of complex traits and diseases in Genes and Health
Dr Hilary Martin, Dr Sarah Finer, Dr Dan Mason, Prof David van Heel
Lay summary
(a) 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
This research will study the link between certain aspects of a person’s genetic makeup and their lifelong health and risk of disease. People of Bangladeshi and Pakistani origin are more likely to develop conditions such as type 2 diabetes and heart disease than people of white European origin. Other common conditions, such as mental health problems (e.g. depression) are also known to affect many people of this heritage, and are important priority topics for further research. Scientists have uncovered many links between genes and health, but there is still a lot to understand. Genes and Health seeks to make new discoveries in this important area and, as such, it hopes to understand better why people of Bangladeshi and Pakistani origin are at high risk of common diseases. Common genetic differences have been linked to many diseases, including diabetes, heart disease and depression. However, these studies have mostly been conducted in individuals from European backgrounds, and it is not well known whether these findings are also relevant to people from Pakistani and Bangladeshi backgrounds. Genes and Health will study whether these findings are relevant to people from Pakistani and Bangladeshi backgrounds, and this will give us opportunities to better understand the causes of disease and predict the chance of a person developing a disease. It is hoped that this knowledge will allow better healthcare to be delivered to people from Bangladeshi and Pakistani backgrounds in the future. Additionally, we plan to look at a particular genetic feature present in some individuals called ‘autozygosity’. Our genes all have two copies, one inherited from the mother, and the other from the father. When a person’s mother and father are related (e.g. cousins) there is a chance that the copies of these genes are the same, and this is called ‘autozygosity’. Autozygosity is more common in people from Bangladeshi and Pakistani backgrounds as it is not unusual for people from these ethnicities to marry and have children within their own families. Studies suggest that autozygosity may affect how genes work predispose to poor health. However, autozygosity has only been studied in relation to certain diseases, and it is not known whether the presence, and amount, of autozygosity in a person’s genetic make-up could cause common diseases such as type 2 diabetes, cardiovascular disease, depression or other mental health conditions. We also want to understand whether autozygosity could affect how severely someone is affected by these conditions if they do occur, and whether they are more or less easy to treat with medication.
b. How will your research improve health?
There is an urgent need to better understand the causes of common diseases that affect people of Bangladeshi and Pakistani origin so that these can be better predicted, prevented, identified and treated. Specifically, our research will improve health in the following ways: - By giving us new scientific understanding of the genetic causes of disease in Pakistani and Bangladeshi people, to enable better prediction of who is at risk and to offer targeted treatment in the future. - To support education and awareness around the causes of disease in people of Bangladeshi and Pakistani origin.
c. How does your research meet the other purposes of Genes and Health?
Our proposal fits with the overall purpose of Genes and Health to better understand the genetic causes of disease in people of Bangladeshi and Pakistani origin, in order to improve health, disease prevention and treatment in the future.
d. Please give a non-technical description of how the research will be undertaken
We will use the following Genes and Health resources: - Genetic information from gene sequencing and genotyping. - Electronic health record data The scientists involved in this project will analyse the genetic information from gene sequencing and genotyping of Genes and Health volunteers. They will perform this work using highly specialised computer-based analysis to identify regions of the genome where ‘autozygosity’ occurs. The scientists will combine this information with insights from electronic health records to see if there is a relationship between autozygosity and disease. Electronic health record data will be used to identify volunteers with a range of different common conditions, including type 2 diabetes, cardiovascular disease and mental health conditions, and look to see if autozygosity is more common in these people than those without autozygosity. The scientists will also investigate whether the location of autozygosity in the genome tells us about the function of particular genes and whether they are responsible for causing disease when they do not work properly. At all times, the researchers and scientists involved in this project will use this information under strict regulations that ensure their work cannot be tracked back to individuals, and is kept fully anonymous.
e. Please state the approximate number of volunteers to be included (i.e. whether the full cohort or a subset)
We anticipate using information from all Genes and Health volunteers participating in Stage 1 where exome sequencing and genotyping is performed.
