Ganjgahi, Habib (2016) Computationally efficient mixed effect model for genetic analysis of high dimensional neuroimaging data. PhD thesis, University of Warwick.

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Abstract

A new research direction in the neuroimaging discipline, so called imaging genetic, has emerged recently concerns describing individual differences in imaging phenotypes using genetic and environmental factors. The large number of voxel- and vertex-wise measurements in imaging genetics studies present a challenge both in terms of computational intensity and the need to account for elevated false positive risk because of the multiple testing problem. There is a gap in existing tools, as standard neuroimaging software cannot perform essential genetic analyses including heritability and association estimations and testings, and yet standard quantitative genetics tools cannot provide essential neuroimaging inferences, like family-wise error corrected voxel- wise or cluster-wise P-values. Moreover, available genetic tools rely on P-values that can be inaccurate with usual parametric inference methods.

In this thesis computationally efficient linear mixed effect model for voxel-wise genetic analyses of high-dimensional imaging phenotypes are developed. Specifically, fast estimation and inference procedures for heritability and association analyses are introduced using orthogonal transformations that dramatically simplify the likelihood and restricted likelihood functions of mixed effect model. We review the family of score, likelihood ratio and Wald tests and propose novel inference methods for fixed and random effect terms in the mixed effect models. To address problems with inaccuracies with the standard results used to find P-values, we propose different permutation schemes to allow semi-parametric inference (parametric likelihood-based estimation, non-parametric sampling distribution). In total, we evaluate different significance tests for heritability and association, with either asymptotic parametric or permutation-based P-value computations. We identify a number of tests that are both computationally efficient and powerful, making them ideal candidates for heritability and genome-wide association studies in the massive data setting.

Item Type:	Thesis or Dissertation (PhD)
Subjects:	Q Science > QA Mathematics R Medicine > RC Internal medicine
Library of Congress Subject Headings (LCSH):	Nervous system -- Imaging, Brain -- Imaging -- Statistical methods, Imaging systems in genetics, Genetics -- Statistical methods, Multilevel models (Statistics)
Official Date:	November 2016
Dates:	Date Event November 2016 Submitted
Institution:	University of Warwick
Theses Department:	Department of Statistics
Thesis Type:	PhD
Publication Status:	Unpublished
Supervisor(s)/Advisor:	Nichols, Thomas E.
Format of File:	pdf
Extent:	xiii, 113 leaves : illustrations, charts
Language:	eng

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