Dataset Information

Sparse group variable selection for gene-environment interactions in the longitudinal study.

ABSTRACT: Penalized variable selection for high-dimensional longitudinal data has received much attention as it can account for the correlation among repeated measurements while providing additional and essential information for improved identification and prediction performance. Despite the success, in longitudinal studies, the potential of penalization methods is far from fully understood for accommodating structured sparsity. In this article, we develop a sparse group penalization method to conduct the bi-level gene-environment (G ×$\times $ E) interaction study under the repeatedly measured phenotype. Within the quadratic inference function framework, the proposed method can achieve simultaneous identification of main and interaction effects on both the group and individual levels. Simulation studies have shown that the proposed method outperforms major competitors. In the case study of asthma data from the Childhood Asthma Management Program, we conduct G ×$\times $ E study by using high-dimensional single nucleotide polymorphism data as genetic factors and the longitudinal trait, forced expiratory volume in 1 s, as the phenotype. Our method leads to improved prediction and identification of main and interaction effects with important implications.

SUBMITTER: Zhou F

PROVIDER: S-EPMC9426288 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Sparse group variable selection for gene-environment interactions in the longitudinal study.

Zhou Fei F Zhou Fei F Lu Xi X Ren Jie J Fan Kun K Ma Shuangge S Wu Cen C

Genetic epidemiology 20220629 5-6

Penalized variable selection for high-dimensional longitudinal data has received much attention as it can account for the correlation among repeated measurements while providing additional and essential information for improved identification and prediction performance. Despite the success, in longitudinal studies, the potential of penalization methods is far from fully understood for accommodating structured sparsity. In this article, we develop a sparse group penalization method to conduct the ...[more]

PMID: 35766061

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Project description:Many existing cohort studies initially designed to investigate disease risk as a function of environmental exposures have collected genomic data in recent years with the objective of testing for gene-environment interaction (G × E) effects. In environmental epidemiology, interest in G × E arises primarily after a significant effect of the environmental exposure has been documented. Cohort studies often collect rich exposure data; as a result, assessing G × E effects in the presence of multiple exposure markers further increases the burden of multiple testing, an issue already present in both genetic and environment health studies. Latent variable (LV) models have been used in environmental epidemiology to reduce dimensionality of the exposure data, gain power by reducing multiplicity issues via condensing exposure data, and avoid collinearity problems due to presence of multiple correlated exposures. We extend the LV framework to characterize gene-environment interaction in presence of multiple correlated exposures and genotype categories. Further, similar to what has been done in case-control G × E studies, we use the assumption of gene-environment (G-E) independence to boost the power of tests for interaction. The consequences of making this assumption, or the issue of how to explicitly model G-E association has not been previously investigated in LV models. We postulate a hierarchy of assumptions about the LV model regarding the different forms of G-E dependence and show that making such assumptions may influence inferential results on the G, E, and G × E parameters. We implement a class of shrinkage estimators to data adaptively trade-off between the most restrictive to most flexible form of G-E dependence assumption and note that such class of compromise estimators can serve as a benchmark of model adequacy in LV models. We demonstrate the methods with an example from the Early Life Exposures in Mexico City to Neuro-Toxicants Study of lead exposure, iron metabolism genes, and birth weight.

Dataset Information

Sparse group variable selection for gene-environment interactions in the longitudinal study.

Publications

Sparse group variable selection for gene-environment interactions in the longitudinal study.

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