Journal article

Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP

S Mead, J Uphill, J Beck, M Poulter, T Campbell, J Lowe, G Adamson, H Hummerich, N Klopp, IM Rückert, HE Wichmann, D Azazi, V Plagnol, WH Pako, J Whitfield, MP Alpers, J Whittaker, DJ Balding, I Zerr, H Kretzschmar Show all

Human Molecular Genetics | Published : 2012

Abstract

Prion diseases are fatal neurodegenerative diseases of humans and animals caused by the misfolding and aggregation of prion protein (PrP). Mammalian prion diseases are under strong genetic control but few risk factors are known aside from the PrP gene locus (PRNP). No genome-wide association study (GWAS) has been done aside from a small sample of variant Creutzfeldt-Jakob disease (CJD). We conducted GWAS of sporadic CJD (sCJD), variant CJD (vCJD), iatrogenic CJD, inherited prion disease, kuru and resistance to kuru despite attendance at mortuary feasts. After quality control, we analysed 2000 samples and 6015 control individuals (provided by the Wellcome Trust Case Control Consortium and KOR..

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University of Melbourne Researchers

Grants

Awarded by Wellcome Trust


Funding Acknowledgements

Funding for the project was provided by the Wellcome Trust and Medical Research Council. The kuru studies were initially funded by a Wellcome Trust Principal Research Fellowship in the Clinical Sciences to J.C., and since 2001, all other aspects of the work by the Medical Research Council. Some of this work was undertaken at UCLH/UCL who received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme. This study makes use of data generated by the Wellcome Trust Case-Control Consortium. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. We would like to thank patients, their families and carers, UK neurologists and other referring physicians, co-workers at the National Prion Clinic, our colleagues at the National Creutzfeldt-Jakob Disease Research and Surveillance Unit, Edinburgh, and the Fore communities in PNG. We thank our team of local kuru reporters, including Tuli Anua, Auyana Winagaiya, the late Anua Senavaiyo, Igana Aresagu, Kabina Yaraki, Anderson Puwa, David Pako, Pibi Auyana, Jolam Ove, Jack Kosinto, Dasta Hutu and James Kisava. We are grateful to Anthony Jackson and Peter Siba, John Reeder, Charles Mgone and other staff of the PNG Institute of Medical Research for their support. We gratefully acknowledge the help of the late Carleton Gajdusek, the late Joseph Gibbs and their associates from the former Laboratory of Central Nervous System Studies of the National Institutes of Health, Bethesda, USA, for archiving and sharing old kuru samples. Genotype data will be made available through the European Genome-phenome Archive.