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Fast and powerful genome wide association of dense genetic data with high dimensional imaging phenotypes

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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41467-018-05444-6

Authors


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Institution:
University of Oxford
Division:
MPLS Division
Department:
Statistics
Role:
Author
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Role:
Author
ORCID:
0000-0002-4169-9781


Publisher:
Nature Publishing Group
Journal:
Nature Communications More from this journal
Volume:
9
Issue:
1
Pages:
3254
Publication date:
2018-08-14
Acceptance date:
2018-07-09
DOI:
EISSN:
2041-1723
Pmid:
30108209


Language:
English
Keywords:
Pubs id:
pubs:908884
UUID:
uuid:58ad1789-edb3-4fed-a496-c4f4127c41ad
Local pid:
pubs:908884
Deposit date:
2018-11-01

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