Approved research

Assessment of rare variants of Mendelian genes in association with traits and/or disease phenotypes in UK Biobank

Lay summary

Some diseases are caused by defects in a single gene where you inherit one bad copy of the gene from each parent. We call this pattern of inheritance Mendelian after the geneticist Gregor Mendel, who first described this pattern of inheritance of traits in pea plants. Other diseases have a more complex pattern of inheritance with minor defects in each of many genes contributing to the disease state. In this study, we will examine whether genes associated with Mendelian diseases might contribute to complex diseases. Some of the rare Mendelian gene mutations found in the cohort can be novel, and we plan to experimentally determine functional impact of novel mutations for a few disease genes we study. This will help us to analyze phenotypic associations with Mendelian genes using only variants that are most likely disease-causing, and it will significantly improve the sensitivity in association analysis. The hope is that if we can find such associations, it might be possible to repurpose existing or develop new drugs for Mendelian disorders to treat more complex diseases. Our research plan is in agreement with the stated aim of UK Biobank 'research intended to improve the prevention, diagnosis and treatment of illness and the promotion of health throughout society'. And we wish to access the full cohort data and carry out our analysis in 3 years.