Dataset Information

Imputation of missing covariate values in epigenome-wide analysis of DNA methylation data.

ABSTRACT: DNA methylation is a widely studied epigenetic mechanism and alterations in methylation patterns may be involved in the development of common diseases. Unlike inherited changes in genetic sequence, variation in site-specific methylation varies by tissue, developmental stage, and disease status, and may be impacted by aging and exposure to environmental factors, such as diet or smoking. These non-genetic factors are typically included in epigenome-wide association studies (EWAS) because they may be confounding factors to the association between methylation and disease. However, missing values in these variables can lead to reduced sample size and decrease the statistical power of EWAS. We propose a site selection and multiple imputation (MI) method to impute missing covariate values and to perform association tests in EWAS. Then, we compare this method to an alternative projection-based method. Through simulations, we show that the MI-based method is slightly conservative, but provides consistent estimates for effect size. We also illustrate these methods with data from the Atherosclerosis Risk in Communities (ARIC) study to carry out an EWAS between methylation levels and smoking status, in which missing cell type compositions and white blood cell counts are imputed.

SUBMITTER: Wu C

PROVIDER: S-EPMC4846117 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Imputation of missing covariate values in epigenome-wide analysis of DNA methylation data.

Wu Chong C Demerath Ellen W EW Pankow James S JS Bressler Jan J Fornage Myriam M Grove Megan L ML Chen Wei W Guan Weihua W

Epigenetics 20160218 2

DNA methylation is a widely studied epigenetic mechanism and alterations in methylation patterns may be involved in the development of common diseases. Unlike inherited changes in genetic sequence, variation in site-specific methylation varies by tissue, developmental stage, and disease status, and may be impacted by aging and exposure to environmental factors, such as diet or smoking. These non-genetic factors are typically included in epigenome-wide association studies (EWAS) because they may ...[more]

PMID: 26890800

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Project description:BACKGROUND:Data collected by an actigraphy device worn on the wrist or waist can provide objective measurements for studies related to physical activity; however, some data may contain intervals where values are missing. In previous studies, statistical methods have been applied to impute missing values on the basis of statistical assumptions. Deep learning algorithms, however, can learn features from the data without any such assumptions and may outperform previous approaches in imputation tasks. OBJECTIVE:The aim of this study was to impute missing values in data using a deep learning approach. METHODS:To develop an imputation model for missing values in accelerometer-based actigraphy data, a denoising convolutional autoencoder was adopted. We trained and tested our deep learning-based imputation model with the National Health and Nutrition Examination Survey data set and validated it with the external Korea National Health and Nutrition Examination Survey and the Korean Chronic Cerebrovascular Disease Oriented Biobank data sets which consist of daily records measuring activity counts. The partial root mean square error and partial mean absolute error of the imputed intervals (partial RMSE and partial MAE, respectively) were calculated using our deep learning-based imputation model (zero-inflated denoising convolutional autoencoder) as well as using other approaches (mean imputation, zero-inflated Poisson regression, and Bayesian regression). RESULTS:The zero-inflated denoising convolutional autoencoder exhibited a partial RMSE of 839.3 counts and partial MAE of 431.1 counts, whereas mean imputation achieved a partial RMSE of 1053.2 counts and partial MAE of 545.4 counts, the zero-inflated Poisson regression model achieved a partial RMSE of 1255.6 counts and partial MAE of 508.6 counts, and Bayesian regression achieved a partial RMSE of 924.5 counts and partial MAE of 605.8 counts. CONCLUSIONS:Our deep learning-based imputation model performed better than the other methods when imputing missing values in actigraphy data.

Dataset Information

Imputation of missing covariate values in epigenome-wide analysis of DNA methylation data.

Publications

Imputation of missing covariate values in epigenome-wide analysis of DNA methylation data.

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