Function-on-function regression for the identification of epigenetic regions exhibiting windows of susceptibility to environmental exposures

DOI10.1214/20-AOAS1425zbMATH Open1478.62358arXiv1912.07359OpenAlexW3204936038MaRDI QIDQ2247489FDOQ2247489

Itai Kloog, Marie-France Hivert, Heike Gibson, Michele Zemplenyi, Brent A. Coull, Sheryl L. Rifas-Shiman, Emily Oken, Mark J. Meyer, Diane R. Gold, Dawn L. Demeo, Joel Schwartz, Andres Cardenas

Publication date: 17 November 2021

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

Abstract: The ability to identify time periods when individuals are most susceptible to exposures, as well as the biological mechanisms through which these exposures act, is of great public health interest. Growing evidence supports an association between prenatal exposure to air pollution and epigenetic marks, such as DNA methylation, but the timing and gene-specific effects of these epigenetic changes are not well understood. Here, we present the first study that aims to identify prenatal windows of susceptibility to air pollution exposures in cord blood DNA methylation. In particular, we propose a function-on-function regression model that leverages data from nearby DNA methylation probes to identify epigenetic regions that exhibit windows of susceptibility to ambient particulate matter less than 2.5 microns (PM${}_{2.5}$). By incorporating the covariance structure among both the multivariate DNA methylation outcome and the time-varying exposure under study, this framework yields greater power to detect windows of susceptibility and greater control of false discoveries than methods that model probes independently. We compare our method to a distributed lag model approach that models DNA methylation in a probe-by-probe manner, both in simulation and by application to motivating data from the Project Viva birth cohort. In two epigenetic regions selected based on prior studies of air pollution effects on epigenome-wide methylation, we identify windows of susceptibility to PM${}_{2.5}$ exposure near the beginning and middle of the third trimester of pregnancy.

Full work available at URL: https://arxiv.org/abs/1912.07359

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zbMATH Keywords

functional data analysiswavelet regressionepigeneticswindows of susceptibility

Mathematics Subject Classification ID

Applications of statistics to environmental and related topics (62P12) Functional data analysis (62R10)

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Cited In (1)

• Heterogeneous Mediation Analysis on Epigenomic PTSD and Traumatic Stress in a Predominantly African American Cohort

Uses Software

• fda (R)
• WaveSeq
• pffr

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