Variants of PLCXD3 are not associated with variant or sporadic Creutzfeldt-Jakob disease in a large international study

Variants of PLCXD3 are not associated with variant or sporadic Creutzfeldt-Jakob disease in a large international study
Balendra, R.; Uphill, J.; Collinson, C.; Druyeh, R.; Adamson, G.; Hummerich, H. & Zerr, I. et al. (2016) 
BMC Medical Genetics17 art. 28.​

Authors
Balendra, Rubika; Uphill, James; Collinson, Claire; Druyeh, Ronald; Adamson, Gary; Hummerich, Holger; Zerr, Inga; Gambetti, Pierluigi; Collinge, John; Mead, Simon
Issue Date
2016
Type
Journal Article
Abstract
Background: Human prion diseases are relentlessly progressive neurodegenerative disorders which include sporadic Creutzfeldt-Jakob disease (sCJD) and variant CJD (vCJD). Aside from variants of the prion protein gene (PRNP) replicated association at genome-wide levels of significance has proven elusive. A recent association study identified variants in or near to the PLCXD3 gene locus as strong disease risk factors in multiple human prion diseases. This study claimed the first non-PRNP locus to be highly significantly associated with prion disease in genomic studies. Methods: A sub-study of a genome-wide association study with imputation aiming to replicate the finding at PLCXD3 including 129 vCJD and 2500 sCJD samples. Whole exome sequencing to identify rare coding variants of PLCXD3. Results: Imputation of relevant polymorphisms was accurate based on wet genotyping of a sample. We found no supportive evidence that PLCXD3 variants are associated with disease. Conclusion: The marked discordance in vCJD genotype frequencies between studies, despite extensive overlap in vCJD cases, and the finding of Hardy-Weinberg disequilibrium in the original study, suggests possible reasons for the discrepancies between studies.
Publisher
Biomed Central Ltd
Journal
BMC Medical Genetics 
ISSN
1471-2350
Publication of Göttingen University
Yes

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