B4727 - Rare variants in PKIG in a UK Birth Cohort - 05/11/2024
B number:
B4727
Principal applicant name:
Stephen O'Rahilly | University of Cambridge (UK)
Co-applicants:
Dr Sam Lockhart
Title of project:
Rare variants in PKIG in a UK Birth Cohort
Proposal summary:
We have found that rare changes in DNA are associated with a diagnosis of heart failure in a large study called UK biobank. In general, these mutations are exceptionally rare in UK Biobank, but we know that the design of UK Biobank can lead to inadvertent exclusion of groups of people which can lead to inaccurate estimates of how common mutations in some genes are. This study, ALSPAC, included the majority of people born during a certain time period in the Avon region. As such, it is less susceptible to some of these problems. As such, we want to use it to refine our estimates of how common these mutations are.
Impact of research:
We think at least two of these genes are possible novel causes of cardiomyopathy acting directly in cardiomyocytes and are testing this hypothesis using association studies in other cohorts and characterisation of a mouse model. This work will help to determine the true prevalence of damaging mutations in these genes and better inform how common/uncommon these mutations are in the general population.
Date proposal received:
Thursday, 24 October, 2024
Date proposal approved:
Tuesday, 5 November, 2024
Keywords:
Genetic epidemiology (including association studies and mendelian randomisation), Cell culture, DNA sequencing, Cardiovascular