Genetics of Schizophrenia. Clozapine: Harnessing the Power of Samples

• Research type

  Research Study

• Full title

  A Large Scale Genetic and Pharmacogenetic study of Clozapine in Schizophrenia

• IRAS ID

  137371

• Contact name

  Gerome Breen

• Sponsor organisation

  King's College London

• Duration of Study in the UK

  4 years, 11 months, 28 days

• Research summary

  There is compelling evidence for a genetic component to schizophrenia, with around 80% of the overall population risk being genetic. This, combined with the complexity and inaccessibility of the brain, suggests that the identification of specific risk genes offers the best chance of understanding the mechanism(s) responsible for this disease. Clozapine, a second generation antipsychotic with superior efficacy where other treatments have failed, shows substantial variability in plasma levels. Such variability observed makes it difficult to predict plasma levels precisely from dose. Existing predictive models of clozapine dose-concentration relationships have produced models of weak to moderate power thus leaving a gap in finding better predictive models. The goal of this project is to use leftover blood from routine plasma clozapine monitoring to augment our current sample resources of subjects with psychosis. The therapeutic monitoring service receives about 25,000 patient samples a year, 90% of which comes from outside the local NHS Trust. The samples represent some 10,000 patients with some 2-3,000 new patients being sampled each year. The two over-arching questions we are aiming to address in this project are, ‘What is the genetic basis of treatment resistant schizophrenia?’ and ‘Can genetic analysis together with other parameters such as age, sex, and dose etc yield meaningful predictive information to, for example, enable patients to avoid weight gain?'

• REC name

  South Central - Berkshire B Research Ethics Committee

• REC reference

  15/SC/0130

• Date of REC Opinion

  23 Feb 2015

• REC opinion

  Favourable Opinion