Wavelet-based genetic association analysis of functional phenotypes arising from high-throughput sequencing assays

DOI10.1214/14-AOAS776zbMATH Open1397.62473arXiv1307.7203WikidataQ49298765 ScholiaQ49298765MaRDI QIDQ746652FDOQ746652

Authors: Heejung Shim, Matthew Stephens 

Publication date: 28 October 2015

Published in: The Annals of Applied Statistics (Search for Journal in Brave)

Abstract: Understanding how genetic variants influence cellular-level processes is an important step towards understanding how they influence important organismal-level traits, or "phenotypes", including human disease susceptibility. To this end scientists are undertaking large-scale genetic association studies that aim to identify genetic variants associated with molecular and cellular phenotypes, such as gene expression, transcription factor binding, or chromatin accessibility. These studies use high-throughput sequencing assays (e.g. RNA-seq, ChIP-seq, DNase-seq) to obtain high-resolution data on how the traits vary along the genome in each sample. However, typical association analyses fail to exploit these high-resolution measurements, instead aggregating the data at coarser resolutions, such as genes, or windows of fixed length. Here we develop and apply statistical methods that better exploit the high-resolution data. The key idea is to treat the sequence data as measuring an underlying "function" that varies along the genome, and then, building on wavelet-based methods for functional data analysis, test for association between genetic variants and the underlying function. Applying these methods to identify genetic variants associated with chromatin accessibility (dsQTLs) we find that they identify substantially more associations than a simpler window-based analysis, and in total we identify 772 novel dsQTLs not identified by the original analysis.

Full work available at URL: https://arxiv.org/abs/1307.7203

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zbMATH Keywords

waveletsfunctional dataBayesian inferencehierarchical modelRNA-seqDNase-seqChIP-seqchromatin accessibilitygenetic association analysishigh-throughput sequencing assays

Mathematics Subject Classification ID

Bayesian inference (62F15) Applications of statistics to biology and medical sciences; meta analysis (62P10) Nontrigonometric harmonic analysis involving wavelets and other special systems (42C40) Protein sequences, DNA sequences (92D20)

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• Title not available (Why is that?)
• Wavelet-based genetic association analysis of functional phenotypes arising from high-throughput sequencing assays

Cited In (6)

• Flexible modelling of genetic effects on function-valued traits
• Multiscale Poisson process approaches for detecting and estimating differences from high-throughput sequencing assays
• Gene level association analysis based on functional linear model
• Wavelet-based genetic association analysis of functional phenotypes arising from high-throughput sequencing assays
• A statistical model to assess (allele-specific) associations between gene expression and epigenetic features using sequencing data
• Analysis of Distributional Variation Through Graphical Multi-Scale Beta-Binomial Models

Uses Software

• qvalue
• WaveSeq
• ChIP-PaM

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