The Annals of Applied Statistics

A functional data analysis approach for genetic association studies

Matthew Reimherr and Dan Nicolae

Full-text: Open access

Abstract

We present a new method based on Functional Data Analysis (FDA) for detecting associations between one or more scalar covariates and a longitudinal response, while correcting for other variables. Our methods exploit the temporal structure of longitudinal data in ways that are otherwise difficult with a multivariate approach. Our procedure, from an FDA perspective, is a departure from more established methods in two key aspects. First, the raw longitudinal phenotypes are assembled into functional trajectories prior to analysis. Second, we explore an association test that is not directly based on principal components. We instead focus on quantifying the reduction in $L^{2}$ variability as a means of detecting associations. Our procedure is motivated by longitudinal genome wide association studies and, in particular, the childhood asthma management program (CAMP) which explores the long term effects of daily asthma treatments. We conduct a simulation study to better understand the advantages (and/or disadvantages) of an FDA approach compared to a traditional multivariate one. We then apply our methodology to data coming from CAMP. We find a potentially new association with a SNP negatively affecting lung function. Furthermore, this SNP seems to have an interaction effect with one of the treatments.

Article information

Source
Ann. Appl. Stat., Volume 8, Number 1 (2014), 406-429.

Dates
First available in Project Euclid: 8 April 2014

Permanent link to this document
https://projecteuclid.org/euclid.aoas/1396966292

Digital Object Identifier
doi:10.1214/13-AOAS692

Mathematical Reviews number (MathSciNet)
MR3191996

Zentralblatt MATH identifier
06302241

Keywords
Functional data analysis longitudinal data analysis genome wide association study functional linear model functional analysis of variance hypothesis testing

Citation

Reimherr, Matthew; Nicolae, Dan. A functional data analysis approach for genetic association studies. Ann. Appl. Stat. 8 (2014), no. 1, 406--429. doi:10.1214/13-AOAS692. https://projecteuclid.org/euclid.aoas/1396966292


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