Pruritus (itch) is characteristic symptom of cholestatic liver disease, including PBC and primary sclerosing cholangitis (PSC). It may be refractory to medical treatment and cause significant reduction in quality of life. The pathogenesis of cholestatic pruritus remains unclear but it may be a complex trait. Identification of genetic factors associated with cholestatic pruritus might help to elucidate its pathogenesis and facilitate development of more effective pharmacotherapy.
The international combined GWAS of cholestatic pruritus is an international collaborative project to identify common variants associated with this trait. There are three phases to the study:
- In Phase 1 (phenotyping), pruritus will be characterised in cases enrolled in ongoing genetic studies of PSC or PBC, using a pruritus questionnaire designed specifically for this study;
- In Phase 2 (discovery), combined, within-case analysis of discovery datasets from GWAS of PSC and GWAS of PBC will be undertaken to identify risk loci for pruritus. Discovery datasets from the following GWAS will be included in this analysis:
- Scandinavian-German GWAS of PSC
- US GWAS of PSC (ongoing)
- UK GWAS of PBC (ongoing)
- Canadian GWAS of PBC
- Italian GWAS of PBC
- UK GWAS of PBC
- In Phase 3 (validation), the index variant at pruritus risk loci will be genotyped in replication cohorts recruited from centres across Europe and North America. Genotyping of replication cohorts will be undertaken at the Wellcome Trust Sanger Institute and Institute of Clinical Molecular Biology (IKMB), Kiel.
Phase 1 of this project (characterisation of pruritus in PSC and PBC cohorts) is ongoing. Phase 2 (combined discovery analysis) will commence in February 2013. It is anticipated that this project will be complete by the end of 2013.
For further information about this study, please contact George Mells