Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies

North American Brain Expression Consortium, Barbara Crain

Research output: Contribution to journalArticle

Abstract

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease. Although an increasing number of genetic factors have been connected to this debilitating condition, the proportion of cases that can be attributed to distinct genetic defects is unknown. To provide a comprehensive analysis of the frequency and spectrum of pathogenic missense mutations and coding risk variants in nine genes previously implicated in DLB, we performed exome sequencing in 111 pathologically confirmed DLB patients. All patients were Caucasian individuals from North America. Allele frequencies of identified missense mutations were compared to 222 control exomes. Remarkably, ~. 25% of cases were found to carry a pathogenic mutation or risk variant in APP, GBA or PSEN1, highlighting that genetic defects play a central role in the pathogenesis of this common neurodegenerative disorder. In total, 13% of our cohort carried a pathogenic mutation in GBA, 10% of cases carried a risk variant or mutation in PSEN1, and 2% were found to carry an APP mutation. The APOE ε4 risk allele was significantly overrepresented in DLB patients (p-value

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalNeurobiology of Disease
Volume94
DOIs
StatePublished - Oct 1 2016

Fingerprint

Lewy Body Disease
Exome
Mutation
Missense Mutation
North America
Gene Frequency
Neurodegenerative Diseases
Dementia
Spectrum Analysis
Alzheimer Disease
Alleles
Genes

Keywords

  • Alzheimer dementia
  • APOE
  • APP
  • Dementia with Lewy bodies
  • Exome sequencing
  • GBA
  • Lewy body dementia
  • PSEN1

ASJC Scopus subject areas

  • Neurology

Cite this

Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies. / North American Brain Expression Consortium; Crain, Barbara.

In: Neurobiology of Disease, Vol. 94, 01.10.2016, p. 55-62.

Research output: Contribution to journalArticle

North American Brain Expression Consortium ; Crain, Barbara. / Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies. In: Neurobiology of Disease. 2016 ; Vol. 94. pp. 55-62.
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