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

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 (...

Full description

Bibliographic Details
Main Authors: Mead, S., Uphill, J., Beck, J., Poulter, M., Campbell, T., Lowe, J., Adamson, G., Hummerich, H., Klopp, N., Ruckert, I., Wichmann, H., Azazu, D., Plagnol, V., Pako, W., Whitfield, J., Alpers, Michael Philip, Whittaker, J., Balding, D., Zerr, I., Kretzschmar, H., Collinge, J.
Format: Journal Article
Published: Oxford University Press 2012
Online Access:http://hdl.handle.net/20.500.11937/47719
_version_ 1848757911065460736
author Mead, S.
Uphill, J.
Beck, J.
Poulter, M.
Campbell, T.
Lowe, J.
Adamson, G.
Hummerich, H.
Klopp, N.
Ruckert, I.
Wichmann, H.
Azazu, D.
Plagnol, V.
Pako, W.
Whitfield, J.
Alpers, Michael Philip
Whittaker, J.
Balding, D.
Zerr, I.
Kretzschmar, H.
Collinge, J.
author_facet Mead, S.
Uphill, J.
Beck, J.
Poulter, M.
Campbell, T.
Lowe, J.
Adamson, G.
Hummerich, H.
Klopp, N.
Ruckert, I.
Wichmann, H.
Azazu, D.
Plagnol, V.
Pako, W.
Whitfield, J.
Alpers, Michael Philip
Whittaker, J.
Balding, D.
Zerr, I.
Kretzschmar, H.
Collinge, J.
author_sort Mead, S.
building Curtin Institutional Repository
collection Online Access
description 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 KORA-gen) for 491032- 511862 SNPs in the European study. Association studies were done in each geographical and aetiological group followed by several combined analyses. The PRNP locus was highly associated with risk in all geographical and aetiological groups. This association was driven by the known coding variation at rs1799990 (PRNP codon 129). No non-PRNP loci achieved genome-wide significance in the meta-analysis of all human prion disease.
first_indexed 2025-11-14T09:35:36Z
format Journal Article
id curtin-20.500.11937-47719
institution Curtin University Malaysia
institution_category Local University
last_indexed 2025-11-14T09:35:36Z
publishDate 2012
publisher Oxford University Press
recordtype eprints
repository_type Digital Repository
spelling curtin-20.500.11937-477192017-09-13T15:58:10Z Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP Mead, S. Uphill, J. Beck, J. Poulter, M. Campbell, T. Lowe, J. Adamson, G. Hummerich, H. Klopp, N. Ruckert, I. Wichmann, H. Azazu, D. Plagnol, V. Pako, W. Whitfield, J. Alpers, Michael Philip Whittaker, J. Balding, D. Zerr, I. Kretzschmar, H. Collinge, J. 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 KORA-gen) for 491032- 511862 SNPs in the European study. Association studies were done in each geographical and aetiological group followed by several combined analyses. The PRNP locus was highly associated with risk in all geographical and aetiological groups. This association was driven by the known coding variation at rs1799990 (PRNP codon 129). No non-PRNP loci achieved genome-wide significance in the meta-analysis of all human prion disease. 2012 Journal Article http://hdl.handle.net/20.500.11937/47719 10.1093/hmg/ddr607 Oxford University Press unknown
spellingShingle Mead, S.
Uphill, J.
Beck, J.
Poulter, M.
Campbell, T.
Lowe, J.
Adamson, G.
Hummerich, H.
Klopp, N.
Ruckert, I.
Wichmann, H.
Azazu, D.
Plagnol, V.
Pako, W.
Whitfield, J.
Alpers, Michael Philip
Whittaker, J.
Balding, D.
Zerr, I.
Kretzschmar, H.
Collinge, J.
Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP
title Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP
title_full Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP
title_fullStr Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP
title_full_unstemmed Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP
title_short Genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to PRNP
title_sort genome-wide association study in multiple human prion diseases suggests genetic risk factors additional to prnp
url http://hdl.handle.net/20.500.11937/47719