Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

Nat Genet. 2021 Mar;53(3):294-303. doi: 10.1038/s41588-021-00785-3. Epub 2021 Feb 15.

Abstract

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Alzheimer Disease / genetics
  • Case-Control Studies
  • Gene Expression Profiling
  • Genetic Predisposition to Disease
  • Genome, Human
  • Genome-Wide Association Study*
  • Glucosylceramidase / genetics
  • Humans
  • Lewy Body Disease / genetics*
  • Nuclear Proteins / genetics
  • Parkinson Disease / genetics
  • Polymorphism, Single Nucleotide
  • Tumor Suppressor Proteins / genetics
  • alpha-Synuclein / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • BIN1 protein, human
  • Nuclear Proteins
  • SNCA protein, human
  • Tumor Suppressor Proteins
  • alpha-Synuclein
  • GBA protein, human
  • Glucosylceramidase

Grants and funding