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Evaluation of Gene-Based Family-Based Methods to Detect Novel Genes Associated With Familial Late Onset Alzheimer Disease.
- Source :
- Frontiers in Neuroscience; 4/4/2018, p1-N.PAG, 19p
- Publication Year :
- 2018
-
Abstract
- Gene-based tests to study the combined effect of rare variants on a particular phenotype have been widely developed for case-control studies, but their evolution and adaptation for family-based studies, especially studies of complex incomplete families, has been slower. In this study, we have performed a practical examination of all the latest gene-based methods available for family-based study designs using both simulated and real datasets. We examined the performance of several collapsing, variance-component, and transmission disequilibrium tests across eight different software packages and 22 models utilizing a cohort of 285 families (N = 1,235) with late-onset Alzheimer disease (LOAD). After a thorough examination of each of these tests, we propose a methodological approach to identify, with high confidence, genes associated with the tested phenotype and we provide recommendations to select the best software and model for family-based gene-based analyses. Additionally, in our dataset, we identified PTK2B, a GWAS candidate gene for sporadic AD, along with six novel genes (CHRD, CLCN2, HDLBP, CPAMD8, NLRP9, and MAS1L) as candidate genes for familial LOAD. [ABSTRACT FROM AUTHOR]
- Subjects :
- GENETICS of Alzheimer's disease
BIOLOGICAL adaptation
BALANCE disorders
Subjects
Details
- Language :
- English
- ISSN :
- 16624548
- Database :
- Complementary Index
- Journal :
- Frontiers in Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 128910273
- Full Text :
- https://doi.org/10.3389/fnins.2018.00209