GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study

Sci Rep. 2019 May 7;9(1):7013. doi: 10.1038/s41598-019-43458-2.

Abstract

Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE ε4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 × 10-8). One additional genetic locus previously linked to psychosis in Alzheimer's disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 × 10-6. We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins E / genetics*
  • Case-Control Studies
  • Europe
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study / methods*
  • Glucosylceramidase / genetics*
  • Humans
  • Iceland
  • Lewy Body Disease / genetics*
  • Norway
  • Nuclear Proteins / genetics
  • Polymorphism, Single Nucleotide*
  • Transcription Factors / genetics

Substances

  • ApoE protein, human
  • Apolipoproteins E
  • Nuclear Proteins
  • Transcription Factors
  • ZFPM1 protein, human
  • GBA protein, human
  • Glucosylceramidase