ArticleThe Lancet. Neurology2009
Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study.
Article in The Lancet. Neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 2 of them syntheses that pooled it.
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Who cites it
76 citing papers in PubMed, 2 syntheses or guidelines pooled it, 153 citations in OpenAlex.
- Network-based SNP meta-analysis identifies joint and disjoint genetic features across common human diseases.BMC genomics · 2012Pooled it
- Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP.Human molecular genetics · 2012Pooled it
- Article
- Accurate genomic predictions for chronic wasting disease in North American elk.G3 (Bethesda, Md.) · 2026Article
- Review
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- Estimating future variant Creutzfeldt-Jakob disease cases in the UK: a cohort-based probabilistic model.The Lancet regional health. Europe · 2025Article
- Human Genetic Evidence for New Targets in Prion Diseases: Opportunities and Challenges.Sub-cellular biochemistry · 2025Review
- Single-cell transcriptomics unveils molecular signatures of neuronal vulnerability in a mouse model of prion disease that overlap with Alzheimer's disease.Nature communications · 2024Article
- Neuropathologically directed profiling of PRNP somatic and germline variants in sporadic human prion disease.Acta neuropathologica · 2024Article
- Neuropathologically-directed profiling ofbioRxiv : the preprint server for biology · 2024Article
- Creutzfeldt-Jakob disease and other prion diseases.Nature reviews. Disease primers · 2024Review
- Article
- Review
- Article
- An arrayed genome-wide perturbation screen identifies the ribonucleoprotein Hnrnpk as rate-limiting for prion propagation.The EMBO journal · 2022Article
- Chronic Wasting Disease (CWD) in Cervids and the Consequences of a Mutable Protein Conformation.ACS omega · 2022Review
- Genetic aspects of human prion diseases.Frontiers in neurology · 2022Review
- Exposure Risk of Chronic Wasting Disease in Humans.Viruses · 2020Review
- Association of chronic wasting disease susceptibility with prion protein variation in white-tailed deer (Prion · 2020Article
16 more citing papers are in PubMed but not listed here.
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15 authors at 3 institutions in 3 countries.
Funding
Abstract
backgroundHuman and animal prion diseases are under genetic control, but apart from PRNP (the gene that encodes the prion protein), we understand little about human susceptibility to bovine spongiform encephalopathy (BSE) prions, the causal agent of variant Creutzfeldt-Jakob disease (vCJD).
methodsWe did a genome-wide association study of the risk of vCJD and tested for replication of our findings in samples from many categories of human prion disease (929 samples) and control samples from the UK and Papua New Guinea (4254 samples), including controls in the UK who were genotyped by the Wellcome Trust Case Control Consortium. We also did follow-up analyses of the genetic control of the clinical phenotype of prion disease and analysed candidate gene expression in a mouse cellular model of prion infection.
findingsThe PRNP locus was strongly associated with risk across several markers and all categories of prion disease (best single SNP [single nucleotide polymorphism] association in vCJD p=2.5 x 10(-17); best haplotypic association in vCJD p=1 x 10(-24)). Although the main contribution to disease risk was conferred by PRNP polymorphic codon 129, another nearby SNP conferred increased risk of vCJD. In addition to PRNP, one technically validated SNP association upstream of RARB (the gene that encodes retinoic acid receptor beta) had nominal genome-wide significance (p=1.9 x 10(-7)). A similar association was found in a small sample of patients with iatrogenic CJD (p=0.030) but not in patients with sporadic CJD (sCJD) or kuru. In cultured cells, retinoic acid regulates the expression of the prion protein. We found an association with acquired prion disease, including vCJD (p=5.6 x 10(-5)), kuru incubation time (p=0.017), and resistance to kuru (p=2.5 x 10(-4)), in a region upstream of STMN2 (the gene that encodes SCG10). The risk genotype was not associated with sCJD but conferred an earlier age of onset. Furthermore, expression of Stmn2 was reduced 30-fold post-infection in a mouse cellular model of prion disease.
interpretationThe polymorphic codon 129 of PRNP was the main genetic risk factor for vCJD; however, additional candidate loci have been identified, which justifies functional analyses of these biological pathways in prion disease.
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