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Prion disease

Implications of new genetic risk factors in prion disease

A genome-wide association study has identified the first risk factors for sporadic prion disease other than mutations of PRNP, which encodes prion protein. These hits could open up new fronts in prion biology, risk prediction, and drug development.

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References

  1. Jones, E. et al. Identification of novel risk loci and causal insights for sporadic Creutzfeldt-Jakob disease: a genome-wide association study. Lancet Neurol. 19, 840–848 (2020).

    Article  CAS  Google Scholar 

  2. Tabrizi, S. J., Flower, M. D., Ross, C. A. & Wild, E. J. Huntington disease: new insights into molecular pathogenesis and therapeutic opportunities. Nat. Rev. Neurol. 16, 529–546 (2020).

    Article  Google Scholar 

  3. Fahed, A. C. et al. Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions. Nat. Commun. 11, 3635 (2020).

    Article  CAS  Google Scholar 

  4. Minikel, E. V. et al. Quantifying prion disease penetrance using large population control cohorts. Sci. Transl Med. 8, 322ra9 (2016).

    Article  Google Scholar 

  5. Minikel, E. V. et al. Age at onset in genetic prion disease and the design of preventive clinical trials. Neurology 93, e125–e134 (2019).

    Article  CAS  Google Scholar 

  6. Nelson, M. R. et al. The support of human genetic evidence for approved drug indications. Nat. Genet. 47, 856–860 (2015).

    Article  CAS  Google Scholar 

  7. Leonenko, G. et al. Genetic risk for alzheimer disease is distinct from genetic risk for amyloid deposition. Ann. Neurol. 86, 427–435 (2019).

    Article  CAS  Google Scholar 

  8. Minikel, E. V. et al. Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints. Nucleic Acids Res. https://doi.org/10.1093/nar/gkaa616 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Vallabh, S. M., Minikel, E. V., Schreiber, S. L. & Lander, E. S. Towards a treatment for genetic prion disease: trials and biomarkers. Lancet Neurol. 19, 361–368 (2020).

    Article  CAS  Google Scholar 

  10. Mok, T. H. & Mead, S. Preclinical biomarkers of prion infection and neurodegeneration. Curr. Opin. Neurobiol. 61, 82–88 (2020).

    Article  CAS  Google Scholar 

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Correspondence to Eric Vallabh Minikel.

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S.M.V. has received speaking fees from Biogen and Illumina, and has received research support in the form of unrestricted charitable contributions from Charles River Laboratories and Ionis Pharmaceuticals. E.V.M. has received consulting fees from Deerfield Management and Guidepoint, and has received research support in the form of unrestricted charitable contributions from Charles River Laboratories and Ionis Pharmaceuticals.

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Vallabh, S.M., Minikel, E.V. Implications of new genetic risk factors in prion disease. Nat Rev Neurol 17, 5–6 (2021). https://doi.org/10.1038/s41582-020-00433-0

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