Familial Hypercholesterolaemia (FH) is a disease of high “bad cholesterol” in blood, which leads to 1 in 5 heart attacks in young people. It is a genetic disease caused by a change (or mutation) in a person’s DNA, that affects 1 in 270 people (~220,000 in the UK). In UK Biobank, 500,000 participants had their entire genetic code (or genome) sequenced. We will search this complete genetic material of UK Biobank individuals to find mutations that cause FH. Our previous findings showed that about half of those who inherit an FH mutation have their “bad cholesterol” within normal range. This suggest that something is protecting those individuals. Although some lifestyle choices, such as diet can have a significant impact on person’s blood cholesterol, we think that sometimes our genes can also have a protective effect. By comparing the genomes of people with an FH mutation but low cholesterol to those with an FH mutation and high cholesterol (as expected in FH patients), we might be able to identify genetic changes in “new” genes, that have a lowering effect on cholesterol. This work is likely to produce knowledge that will support the development of new cholesterol-lowering treatments that can benefit many people at risk of heart attack. This work will be completed within 36 months.
