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

BMC Med Genet. 2016 Apr 7;17:28. doi: 10.1186/s12881-016-0278-2.


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.

Keywords: Creutzfeldt-Jakob disease; Human prion diseases; PLCXD3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Creutzfeldt-Jakob Syndrome / diagnosis
  • Creutzfeldt-Jakob Syndrome / genetics*
  • Exons
  • Genetic Loci
  • Genome-Wide Association Study
  • Genotyping Techniques
  • Germany
  • Humans
  • Linkage Disequilibrium
  • Phosphoinositide Phospholipase C / genetics*
  • Polymorphism, Single Nucleotide*
  • Prion Proteins
  • Prions / genetics
  • Prions / metabolism
  • Risk Factors
  • United States


  • PRNP protein, human
  • Prion Proteins
  • Prions
  • Phosphoinositide Phospholipase C
  • phosphatidylinositol specific phospholipase C, human

Supplementary concepts

  • Creutzfeldt-Jakob Disease, Sporadic