1. Ordered Subset Analysis of Copy Number Variation Association with Age at Onset of Alzheimer's Disease.
- Author
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Szigeti, Kinga, Kellermayer, Blanka, Lentini, Jenna M., Trummer, Brian, Lal, Deepika, Doody, Rachelle S., Yan, Li, Liu, Song, and Ma, Changxing
- Subjects
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AGE of onset , *ALZHEIMER'S disease , *ENDOCYTOSIS , *NEURODEGENERATION , *MEDICAL genetics , *GENETICS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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