Genome-wide study of human prion disease. (360G-Wellcome-084701_Z_08_Z)

We propose a genome-wide association study of human prion disease using a collection of over 3000 patient samples. The discovery phase of the study comprises ~1500 sporadic CJD samples from the UK and Germany compared with large samples of publicly available population control genotype data. The replication phase will test the top 1500 single-SNP based associations with the best of four genetic models in a further cohort of over 2000 samples including sporadic CJD and controls from multiple European CJD reference centres and collections of acquired prion disease (variant CJD, kuru and resistance to kuru) from the UK and Papua New Guinea. The rationale for the study design is that it incorporates both the statistical power afforded by large sample collections of sporadic CJD with the public health importance of the acquired prion diseases. Our analysis will include tests of genotyping quality and will assess population structure between the two contributing cohorts of the discovery phase. We have established expertise in conducting GWAS, data management and statistical analysis. In the circumstance that we are funded to conduct our study independent of the WTCCC we plan that within 12 months of the start of the study we aim to have completed genotyping of the discovery phase using Illumina 550 bead arrays and have chosen the candidate SNPs for replication study. Within 18 months we aim to have completed both phases of the study.