Claringbould Lab

Department                        Internal Medicine

Principal investigator      Annique Claringbould

E-mail address                   a.claringbould@erasmusmc.nl

Website                               https://www.erasmusmc.nl/en/research/researchers/claringbould-annique

 

Integrative genetic scoring for personalised risk assessment of Familial Hypercholesterolaemia

Supervisor: Annique Claringbould, a.claringbould@erasmusmc.nl

Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated blood cholesterol levels from birth, which increases the risk of cardiovascular disease (CVD). While FH is diagnosed by finding mutations in the LDLR, APOB, and PCSK9 genes, recent genome-wide association studies (GWAS) have highlighted the role of common genetic variants in lipid metabolism. When combined, these variants have a big impact on lipid levels.

In this project, we will develop a score that integrates rare mutations, common variants, and molecular variants to provide a comprehensive genetic risk assessment for FH patients. We will use data from the large-scale UK Biobank and a cohort of FH patients with early CVD. This approach aims to improve the prediction of clinical outcomes for FH patients and contribute to personalized treatment.

Techniques

  • Programming in R and on a server (linux-based) (no experience required)
  • Calculation of polygenic scores
  • Identifying strucural variation and calling rare variants in whole exome data

Further reading

Võsa U*, Claringbould A*, Westra HJ, et al. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression. Nat Genet 2021 539. 2021;53(9):1300-1310. doi:10.1038/s41588-021-00913-z