Dataset Information

A Systematic Comparison of Linear Regression-Based Statistical Methods to Assess Exposome-Health Associations.

ABSTRACT:

Background

The exposome constitutes a promising framework to improve understanding of the effects of environmental exposures on health by explicitly considering multiple testing and avoiding selective reporting. However, exposome studies are challenged by the simultaneous consideration of many correlated exposures.

Objectives

We compared the performances of linear regression-based statistical methods in assessing exposome-health associations.

Methods

In a simulation study, we generated 237 exposure covariates with a realistic correlation structure and with a health outcome linearly related to 0 to 25 of these covariates. Statistical methods were compared primarily in terms of false discovery proportion (FDP) and sensitivity.

Results

On average over all simulation settings, the elastic net and sparse partial least-squares regression showed a sensitivity of 76% and an FDP of 44%; Graphical Unit Evolutionary Stochastic Search (GUESS) and the deletion/substitution/addition (DSA) algorithm revealed a sensitivity of 81% and an FDP of 34%. The environment-wide association study (EWAS) underperformed these methods in terms of FDP (average FDP, 86%) despite a higher sensitivity. Performances decreased considerably when assuming an exposome exposure matrix with high levels of correlation between covariates.

Conclusions

Correlation between exposures is a challenge for exposome research, and the statistical methods investigated in this study were limited in their ability to efficiently differentiate true predictors from correlated covariates in a realistic exposome context. Although GUESS and DSA provided a marginally better balance between sensitivity and FDP, they did not outperform the other multivariate methods across all scenarios and properties examined, and computational complexity and flexibility should also be considered when choosing between these methods. Citation: Agier L, Portengen L, Chadeau-Hyam M, Basagaña X, Giorgis-Allemand L, Siroux V, Robinson O, Vlaanderen J, González JR, Nieuwenhuijsen MJ, Vineis P, Vrijheid M, Slama R, Vermeulen R. 2016. A systematic comparison of linear regression-based statistical methods to assess exposome-health associations. Environ Health Perspect 124:1848-1856;?http://dx.doi.org/10.1289/EHP172.

SUBMITTER: Agier L

PROVIDER: S-EPMC5132632 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Publications

A Systematic Comparison of Linear Regression-Based Statistical Methods to Assess Exposome-Health Associations.

Agier Lydiane L Portengen Lützen L Chadeau-Hyam Marc M Basagaña Xavier X Giorgis-Allemand Lise L Siroux Valérie V Robinson Oliver O Vlaanderen Jelle J González Juan R JR Nieuwenhuijsen Mark J MJ Vineis Paolo P Vrijheid Martine M Slama Rémy R Vermeulen Roel R

Environmental health perspectives 20160524 12

<h4>Background</h4>The exposome constitutes a promising framework to improve understanding of the effects of environmental exposures on health by explicitly considering multiple testing and avoiding selective reporting. However, exposome studies are challenged by the simultaneous consideration of many correlated exposures.<h4>Objectives</h4>We compared the performances of linear regression-based statistical methods in assessing exposome-health associations.<h4>Methods</h4>In a simulation study, ...[more]

PMID: 27219331

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Project description:BackgroundThere is growing interest in examining the simultaneous effects of multiple exposures and, more generally, the effects of mixtures of exposures, as part of the exposome concept (being defined as the totality of human environmental exposures from conception onwards). Uncovering such combined effects is challenging owing to the large number of exposures, several of them being highly correlated. We performed a simulation study in an exposome context to compare the performance of several statistical methods that have been proposed to detect statistical interactions.MethodsSimulations were based on an exposome including 237 exposures with a realistic correlation structure. We considered several statistical regression-based methods, including two-step Environment-Wide Association Study (EWAS2), the Deletion/Substitution/Addition (DSA) algorithm, the Least Absolute Shrinkage and Selection Operator (LASSO), Group-Lasso INTERaction-NET (GLINTERNET), a three-step method based on regression trees and finally Boosted Regression Trees (BRT). We assessed the performance of each method in terms of model size, predictive ability, sensitivity and false discovery rate.ResultsGLINTERNET and DSA had better overall performance than the other methods, with GLINTERNET having better properties in terms of selecting the true predictors (sensitivity) and of predictive ability, while DSA had a lower number of false positives. In terms of ability to capture interaction terms, GLINTERNET and DSA had again the best performances, with the same trade-off between sensitivity and false discovery proportion. When GLINTERNET and DSA failed to select an exposure truly associated with the outcome, they tended to select a highly correlated one. When interactions were not present in the data, using variable selection methods that allowed for interactions had only slight costs in performance compared to methods that only searched for main effects.ConclusionsGLINTERNET and DSA provided better performance in detecting two-way interactions, compared to other existing methods.

Project description:This paper concerns the folded concave penalized sparse linear regression (FCPSLR), a class of popular sparse recovery methods. Although FCPSLR yields desirable recovery performance when solved globally, computing a global solution is NP-complete. Despite some existing statistical performance analyses on local minimizers or on specific FCPSLR-based learning algorithms, it still remains open questions whether local solutions that are known to admit fully polynomial-time approximation schemes (FPTAS) may already be sufficient to ensure the statistical performance, and whether that statistical performance can be non-contingent on the specific designs of computing procedures. To address the questions, this paper presents the following threefold results: (i) Any local solution (stationary point) is a sparse estimator, under some conditions on the parameters of the folded concave penalties. (ii) Perhaps more importantly, any local solution satisfying a significant subspace second-order necessary condition (S3ONC), which is weaker than the second-order KKT condition, yields a bounded error in approximating the true parameter with high probability. In addition, if the minimal signal strength is sufficient, the S3ONC solution likely recovers the oracle solution. This result also explicates that the goal of improving the statistical performance is consistent with the optimization criteria of minimizing the suboptimality gap in solving the non-convex programming formulation of FCPSLR. (iii) We apply (ii) to the special case of FCPSLR with minimax concave penalty (MCP) and show that under the restricted eigenvalue condition, any S3ONC solution with a better objective value than the Lasso solution entails the strong oracle property. In addition, such a solution generates a model error (ME) comparable to the optimal but exponential-time sparse estimator given a sufficient sample size, while the worst-case ME is comparable to the Lasso in general. Furthermore, to guarantee the S3ONC admits FPTAS.

Project description:BackgroundEnvironmental Enteropathy (EE) is a subclinical condition caused by constant fecal-oral contamination and resulting in blunting of intestinal villi and intestinal inflammation. Of primary interest in the clinical research is to evaluate the association between non-invasive EE biomarkers and malnutrition in a cohort of Bangladeshi children. The challenges are that the number of biomarkers/covariates is relatively large, and some of them are highly correlated.MethodsMany variable selection methods are available in the literature, but which are most appropriate for EE biomarker selection remains unclear. In this study, different variable selection approaches were applied and the performance of these methods was assessed numerically through simulation studies, assuming the correlations among covariates were similar to those in the Bangladesh cohort. The suggested methods from simulations were applied to the Bangladesh cohort to select the most relevant biomarkers for the growth response, and bootstrapping methods were used to evaluate the consistency of selection results.ResultsThrough simulation studies, SCAD (Smoothly Clipped Absolute Deviation), Adaptive LASSO (Least Absolute Shrinkage and Selection Operator) and MCP (Minimax Concave Penalty) are the suggested variable selection methods, compared to traditional stepwise regression method. In the Bangladesh data, predictors such as mother weight, height-for-age z-score (HAZ) at week 18, and inflammation markers (Myeloperoxidase (MPO) at week 12 and soluable CD14 at week 18) are informative biomarkers associated with children's growth.ConclusionsPenalized linear regression methods are plausible alternatives to traditional variable selection methods, and the suggested methods are applicable to other biomedical studies. The selected early-stage biomarkers offer a potential explanation for the burden of malnutrition problems in low-income countries, allow early identification of infants at risk, and suggest pathways for intervention.Trial registrationThis study was retrospectively registered with ClinicalTrials.gov, number NCT01375647, on June 3, 2011.

Dataset Information

A Systematic Comparison of Linear Regression-Based Statistical Methods to Assess Exposome-Health Associations.

Background

Objectives

Methods

Results

Conclusions

Publications

A Systematic Comparison of Linear Regression-Based Statistical Methods to Assess Exposome-Health Associations.

Similar Datasets

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