Oligogenic genetic variation of neurodegenerative disease genes in 980 postmortem human brains.

ABSTRACT:

Background

Several studies suggest that multiple rare genetic variants in genes causing monogenic forms of neurodegenerative disorders interact synergistically to increase disease risk or reduce the age of onset, but these studies have not been validated in large sporadic case series.

Methods

We analysed 980 neuropathologically characterised human brains with Alzheimer's disease (AD), Parkinson's disease-dementia with Lewy bodies (PD-DLB), frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) and age-matched controls. Genetic variants were assessed using the American College of Medical Genetics criteria for pathogenicity. Individuals with two or more variants within a relevant disease gene panel were defined as 'oligogenic'.

Results

The majority of oligogeni

SUBMITTER: Keogh MJ 

PROVIDER: S-EPMC6204946 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature