Dataset Information

Structured gene-environment interaction analysis.

ABSTRACT: For the etiology, progression, and treatment of complex diseases, gene-environment (G-E) interactions have important implications beyond the main G and E effects. G-E interaction analysis can be more challenging with higher dimensionality and need for accommodating the "main effects, interactions" hierarchy. In recent literature, an array of novel methods, many of which are based on the penalization technique, have been developed. In most of these studies, however, the structures of G measurements, for example, the adjacency structure of single nucleotide polymorphisms (SNPs; attributable to their physical adjacency on the chromosomes) and the network structure of gene expressions (attributable to their coordinated biological functions and correlated measurements) have not been well accommodated. In this study, we develop structured G-E interaction analysis, where such structures are accommodated using penalization for both the main G effects and interactions. Penalization is also applied for regularized estimation and selection. The proposed structured interaction analysis can be effectively realized. It is shown to have consistency properties under high-dimensional settings. Simulations and analysis of GENEVA diabetes data with SNP measurements and TCGA melanoma data with gene expression measurements demonstrate its competitive practical performance.

SUBMITTER: Wu M

PROVIDER: S-EPMC7028505 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Structured gene-environment interaction analysis.

Wu Mengyun M Zhang Qingzhao Q Ma Shuangge S

Biometrics 20191009 1

For the etiology, progression, and treatment of complex diseases, gene-environment (G-E) interactions have important implications beyond the main G and E effects. G-E interaction analysis can be more challenging with higher dimensionality and need for accommodating the "main effects, interactions" hierarchy. In recent literature, an array of novel methods, many of which are based on the penalization technique, have been developed. In most of these studies, however, the structures of G measuremen ...[more]

PMID: 31424088

Similar Datasets

Project description:Genotype-by-environment interaction (GxE) studies probe heterogeneity in response to risk factors or interventions. Popular methods for estimation of GxE examine multiplicative interactions between individual genetic and environmental measures. However, risk factors and interventions may modulate the total variance of an epidemiological outcome that itself represents the aggregation of many other etiological components. We expand the traditional GxE model to directly model genetic and environmental moderation of the dispersion of the outcome. We derive a test statistic, [Formula: see text], for inferring whether an interaction identified between individual genetic and environmental measures represents a more general pattern of moderation of the total variance in the phenotype by either the genetic or the environmental measure. We validate our method via extensive simulation, and apply it to investigate genotype-by-birth year interactions for Body Mass Index (BMI) with polygenic scores in the Health and Retirement Study (N = 11,586) and individual genetic variants in the UK Biobank (N = 380,605). We find that changes in the penetrance of a genome-wide polygenic score for BMI across birth year are partly representative of a more general pattern of expanding BMI variation across generations. Three individual variants found to be more strongly associated with BMI among later born individuals, were also associated with the magnitude of variability in BMI itself within any given birth year, suggesting that they may confer general sensitivity of BMI to a range of unmeasured factors beyond those captured by birth year. We introduce an expanded GxE regression model that explicitly models genetic and environmental moderation of the dispersion of the outcome under study. This approach can determine whether GxE interactions identified are specific to the measured predictors or represent a more general pattern of moderation of the total variance in the outcome by the genetic and environmental measures.

Dataset Information

Structured gene-environment interaction analysis.

Publications

Structured gene-environment interaction analysis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets