Genetic Risk Factors for Variant Creutzfeldt–Jakob Disease
Author Information
Author(s): Simon Mead, Mark Poulter, James Uphill, John Beck, Jerome Whitfield, Thomas Webb, Tracy Campbell, Gary Adamson, Pelagia Deriziotis, Sarah Tabrizi, Holger Hummerich, Claudio Verzilli, Michael Alpers, John Whittaker, John Collinge
Primary Institution: Medical Research Council Prion Unit and Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London, UK
Hypothesis
What genetic factors contribute to the risk of variant Creutzfeldt–Jakob disease (vCJD)?
Conclusion
The study identified the PRNP codon 129 as the main genetic risk factor for vCJD, along with additional candidate loci.
Supporting Evidence
- The PRNP locus was strongly associated with risk across several markers.
- Best single SNP association in vCJD was p=2·5×10−17.
- Another SNP upstream of RARB had nominal genome-wide significance (p=1·9×10−7).
- Expression of Stmn2 was reduced 30-fold post-infection in a mouse model.
Takeaway
Scientists found that a specific gene is linked to a disease called variant Creutzfeldt–Jakob disease, which can be caused by eating infected meat.
Methodology
A genome-wide association study was conducted with samples from patients with vCJD and various control groups.
Potential Biases
Potential bias due to the rarity of the disease and the use of amplified DNA in some cases.
Limitations
The study's power was limited by the small size of the vCJD sample and the use of an early generation platform.
Participant Demographics
Patients were primarily white British, with a mean age of disease onset of 29.8 years for vCJD.
Statistical Information
P-Value
p=2·5×10−17
Confidence Interval
95% CI 9·6–155·2
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
Want to read the original?
Access the complete publication on the publisher's website