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Fast and powerful genome wide association of dense genetic data with high dimensional imaging phenotypes
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Ganjgahi, Habib, Winkler, Anderson M., Glahn, David C., Blangero, John, Donohue, Brian, Kochunov, Peter and Nichols, Thomas E. (2018) Fast and powerful genome wide association of dense genetic data with high dimensional imaging phenotypes. Nature Communications, 9 (1). 3254. doi:10.1038/s41467-018-05444-6 ISSN 2041-1723.
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Official URL: https://doi.org/10.1038/s41467-018-05444-6
Abstract
Genome wide association (GWA) analysis of brain imaging phenotypes can advance our understanding of the genetic basis of normal and disorder-related variation in the brain. GWA approaches typically use linear mixed effect models to account for non-independence amongst subjects due to factors, such as family relatedness and population structure. The use of these models with high-dimensional imaging phenotypes presents enormous challenges in terms of computational intensity and the need to account multiple testing in both the imaging and genetic domain. Here we present a method that makes mixed models practical with high-dimensional traits by a combination of a transformation applied to the data and model, and the use of a non-iterative variance component estimator. With such speed enhancements permutation tests are feasible, which allows inference on powerful spatial tests like the cluster size statistic.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Statistics | ||||||
SWORD Depositor: | Library Publications Router | ||||||
Journal or Publication Title: | Nature Communications | ||||||
Publisher: | Nature Publishing Group | ||||||
ISSN: | 2041-1723 | ||||||
Official Date: | 14 August 2018 | ||||||
Dates: |
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Volume: | 9 | ||||||
Number: | 1 | ||||||
Article Number: | 3254 | ||||||
DOI: | 10.1038/s41467-018-05444-6 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
Date of first compliant deposit: | 25 September 2018 |
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