Title | Evaluation of Gene-Based Family-Based Methods to Detect Novel Genes Associated With Familial Late Onset Alzheimer Disease. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Fernández MV, Budde J, Del-Aguila JL, Ibañez L, Deming Y, Harari O, Norton J, Morris JC, Goate AM, Cruchaga C |
Corporate Authors | NIA-LOAD family study group, NCRAD |
Journal | Front Neurosci |
Volume | 12 |
Pagination | 209 |
Date Published | 2018 |
ISSN | 1662-4548 |
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 ( = 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 , a GWAS candidate gene for sporadic AD, along with six novel genes (, and ) as candidate genes for familial LOAD. |
DOI | 10.3389/fnins.2018.00209 |
Pubmed Link | http://www.ncbi.nlm.nih.gov/pubmed/29670507?dopt=Abstract |
page_expo | External |
Alternate Journal | Front Neurosci |
PubMed ID | 29670507 |
PubMed Central ID | PMC5893779 |
Grant List | R01 AG058501 / AG / NIA NIH HHS / United States U24 AG021886 / AG / NIA NIH HHS / United States P01 AG003991 / AG / NIA NIH HHS / United States P50 AG005681 / AG / NIA NIH HHS / United States P01 AG026276 / AG / NIA NIH HHS / United States R25 DA027995 / DA / NIDA NIH HHS / United States |
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