Genetic association of high-dimensional traits
type: CreativeWork
description: Over the past ten years, more than 4,000 genome-wide association studies (GWAS) have helped to shed light on the genetic architecture of complex traits and diseases. In recent years, phenotyping of the samples has often gone beyond single traits and it has become common to record multi- to high-dimensional phenotypes for individu- als. Whilst these rich datasets offer the potential to analyse complex trait structures and pleiotropic effects at a genome-wide level, novel analytic challenges arise. This thesis summarises my research into genetic associations for high-dimensional phen- otype data. First, I developed a novel and computationally efficient approach for multivari- ate analysis of high-dimensional phenotypes based on linear mixed models, com- bined with bootstrapping (LiMMBo). Both in simulation studies and on real data, I demonstrate the statistical validity of LiMMBo and that it can scale to hundreds of phenotypes. I show the gain in power of multivariate analyses for high-dimensional phenotypes compared to univariate approaches, and illustrate that LiMMBo allows for detecting pleiotropy in a large number of phenotypic traits. Aside from their computational challenges in GWAS, the true dimensionality of very high-dimensional phenotypes is often unknown and lies hidden in high-dimen- sional space. Retaining maximum power for association studies of such phenotype data relies on using an appropriate phenotype representation. I systematically ana- lysed twelve unsupervised dimensionality reduction methods based on their per- formance in finding a robust phenotype representation in simulated data of different structure and size. I propose a stability criteria for choosing low-dimensional phen- otype representations and demonstrate that stable phenotypes can recover genetic associations. Finally, I analysed genetic variants for associations to high-dimensional cardiac phenotypes based on MRI data from 1,500 healthy individuals. I used an unsuper- vised approach…
abstract: Over the past ten years, more than 4,000 genome-wide association studies (GWAS) have helped to shed light on the genetic architecture of complex traits and diseases. In recent years, phenotyping of the samples has often gone beyond single traits and it has become common to record multi- to high-dimensional phenotypes for individu- als. Whilst these rich datasets offer the potential to analyse complex trait structures and pleiotropic effects at a genome-wide level, novel analytic challenges arise. This thesis summarises my research into genetic associations for high-dimensional phen- otype data. First, I developed a novel and computationally efficient approach for multivari- ate analysis of high-dimensional phenotypes based on linear mixed models, com- bined with bootstrapping (LiMMBo). Both in simulation studies and on real data, I demonstrate the statistical validity of LiMMBo and that it can scale to hundreds of phenotypes. I show the gain in power of multivariate analyses for high-dimensional phenotypes compared to univariate approaches, and illustrate that LiMMBo allows for detecting pleiotropy in a large number of phenotypic traits. Aside from their computational challenges in GWAS, the true dimensionality of very high-dimensional phenotypes is often unknown and lies hidden in high-dimen- sional space. Retaining maximum power for association studies of such phenotype data relies on using an appropriate phenotype representation. I systematically ana- lysed twelve unsupervised dimensionality reduction methods based on their per- formance in finding a robust phenotype representation in simulated data of different structure and size. I propose a stability criteria for choosing low-dimensional phen- otype representations and demonstrate that stable phenotypes can recover genetic associations. Finally, I analysed genetic variants for associations to high-dimensional cardiac phenotypes based on MRI data from 1,500 healthy individuals. I used an unsuper- vised approach…
author: Meyer, Hannah Verena
language: en
keywords: Genomics, Imaging Genetics, GWAS, Dimensionality Reduction, Linear Mixed Models, High-dimensional phenotypes, Simulation, Model development, Cardiac Biology
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/ff99da4f-168e-4f82-aba2-dc75c05da387/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2019-06-30
date modified: 2026-07-22T22:24:10Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.26456