Current Research

Long-term Follow Up: 

Earlier results from the register emphasised the importance of early identification of FH and treatment with statins. We now wish to extend our previous reports to include events for an enlarged cohort followed for up to 34 years, giving us increased power and allowing us to examine more informatively the changes in mortality compared with the general population before and after the routine use of statins. We have recently obtained the necessary regulatory approval for obtaining the mortality data from the office of National Statistics and plan to carry out this analysis by the end of 2015.

Identifying novel genes causing FH:

We have been analysing complete exome sequencing data on 125 FH patients as part of the UK 10K project.  The analytical strategy we have been using is firstly to look for variation in all known FH causing genes (LDLR/APOB/PCSK9). The second stage is to analyse all those genes where a common DNA variant is associated with effects on LDL-C levels.  The third stage of analysis is to look at every annotated gene in the entire genome!   For the second and third analyses, the statistical approach is to compare the frequency of variants called by the software as definite or probable FH causing (loss of function or affecting function, e.g. stop codons, and missense called as probably pathogenic) between the FH group and the group of other individuals who have also been part of the sequencing project, but who do not have an abnormal lipid phenotype.  Any gene where there are a significantly higher number of such functional variants in the FH patients compared to the controls are worthy of follow up.   In the current analysis we do not have strong evidence for any such novel gene (17), but If any such gene is identified (or if a fourth FH causing gene is published), we will follow them up with detailed molecular biology, and genetic epidemiology studies using the extensive FH cohort samples we have available.

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Learn about the history of Simon Broome