Ordered Subset Analysis of Copy Number Variation Association with Age at Onset of Alzheimer's Disease
Year: 2014
Type: article
Study design: Observational Study
Abstract: Genetic heterogeneity is a common problem for genome-wide association studies of complex human diseases. Ordered-subset analysis (OSA) reduces genetic heterogeneity and optimizes the use of phenotypic information, thus improving power under some disease models. We hypothesized that in a genetically heterogeneous disorder such as Alzheimer's disease (AD), utilizing OSA by age at onset (AAO) of AD may increase the power to detect relevant loci. Using this approach, 8 loci were detected, including the chr15 : 30,44 region harboring CHRFAM7A. The association was replicated in the NIA-LOAD Familial Study dataset. CHRFAM7A is a dominant negative regulator of CHRNA7 function, the receptor that facilitates amyloid-β1-42 internalization through endocytosis and has been implicated in AD. OSA, using AAO as a quantitative trait, optimized power and detected replicable signals suggesting that AD is genetically heterogeneous between AAO subsets.
Source: Journal of Alzheimer s Disease
DOI: 10.3233/jad-132693
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Institute on Aging
Awards: OLFACTORY RECEPTOR COPY NUMBER ASSOCIATION WITH AGE AT ONSET OF ALZHEIMER DISEASE, Epidemiology of Familial Late-Onset Alzheimer's Disease, National Institute on Aging Alzheimer's Disease Family-Based Study (NIA-AD FBS), National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)
OpenAlex ID: W1577203367