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Population Pharmacogenetics of statin response

Colin Palmer

Andrew Morris, Ewan Pearson, Alex Doney.

Statin lipid lowering drugs are prescribed to a very large proportion of the aging population, and these are the key drugs in preventing the onset of cardiovascular disease. However it is known that there is considerable inter-individual variation in the response to these drugs. It is possible that genetic testing may allow for a more informed approach to the usage of these drugs and may guide the dosage to be used of this drug to be used in individuals to maximize the efficacy and safety of the drug for each patient.

We propose to take advantage of the recent advances in genotyping tenchology and to apply this to the area of pharmacogenetics and to define loci responsible for modulating inter-individual differences in response to the statin group of lipid lowering drugs. We plan to:

  1. Perform whole genome association analysis in a large population of 4000 individuals with T2D who have been treated with statins. We will use sophisticated health informatics, only available in Tayside to define a longitudinal, repeated measures, cholesterol response to statin
  2. Perform replication studies in-silico by data-sharing with clinical-trial based WGA studies (N>3000) to ensure robust identification of the principal response SNPs.
  3. We will take the 150 variants with the most compelling association signals from this combined analysis through another round of replication involving another 2,000 Tayside-based samples.

This study is uniquely placed to deliver insights into the potential for personalized medicine, and to initiate the task of translating those findings into advances in clinical care.