Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

FEATURE SELECTION FOR GENERALIZED VARYING COEFFICIENT MIXED-EFFECT MODELS WITH APPLICATION TO OBESITY GWAS.

ABSTRACT: Motivated by an empirical analysis of data from a genome-wide association study on obesity, measured by the body mass index (BMI), we propose a two-step gene-detection procedure for generalized varying coefficient mixed-effects models with ultrahigh dimensional covariates. The proposed procedure selects significant single nucleotide polymorphisms (SNPs) impacting the mean BMI trend, some of which have already been biologically proven to be "fat genes." The method also discovers SNPs that significantly influence the age-dependent variability of BMI. The proposed procedure takes into account individual variations of genetic effects and can also be directly applied to longitudinal data with continuous, binary or count responses. We employ Monte Carlo simulation studies to assess the performance of the proposed method and further carry out causal inference for the selected SNPs.

SUBMITTER: Chu W

PROVIDER: S-EPMC7426018 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

FEATURE SELECTION FOR GENERALIZED VARYING COEFFICIENT MIXED-EFFECT MODELS WITH APPLICATION TO OBESITY GWAS.

Chu Wanghuan W Li Runze R Liu Jingyuan J Reimherr Matthew M

The annals of applied statistics 20200301 1

Motivated by an empirical analysis of data from a genome-wide association study on obesity, measured by the body mass index (BMI), we propose a two-step gene-detection procedure for generalized varying coefficient mixed-effects models with ultrahigh dimensional covariates. The proposed procedure selects significant single nucleotide polymorphisms (SNPs) impacting the mean BMI trend, some of which have already been biologically proven to be "fat genes." The method also discovers SNPs that signifi ...[more]

PMID: 32802245

Similar Datasets

Feature Selection for Varying Coefficient Models With Ultrahigh Dimensional Covariates.

Project description:This paper is concerned with feature screening and variable selection for varying coefficient models with ultrahigh dimensional covariates. We propose a new feature screening procedure for these models based on conditional correlation coefficient. We systematically study the theoretical properties of the proposed procedure, and establish their sure screening property and the ranking consistency. To enhance the finite sample performance of the proposed procedure, we further develop an iterative feature screening procedure. Monte Carlo simulation studies were conducted to examine the performance of the proposed procedures. In practice, we advocate a two-stage approach for varying coefficient models. The two stage approach consists of (a) reducing the ultrahigh dimensionality by using the proposed procedure and (b) applying regularization methods for dimension-reduced varying coefficient models to make statistical inferences on the coefficient functions. We illustrate the proposed two-stage approach by a real data example.

| S-EPMC3963210 | biostudies-literature

Penalized Quadratic Inference Function-Based Variable Selection for Generalized Partially Linear Varying Coefficient Models with Longitudinal Data.

Project description:Semiparametric generalized varying coefficient partially linear models with longitudinal data arise in contemporary biology, medicine, and life science. In this paper, we consider a variable selection procedure based on the combination of the basis function approximations and quadratic inference functions with SCAD penalty. The proposed procedure simultaneously selects significant variables in the parametric components and the nonparametric components. With appropriate selection of the tuning parameters, we establish the consistency, sparsity, and asymptotic normality of the resulting estimators. The finite sample performance of the proposed methods is evaluated through extensive simulation studies and a real data analysis.

| S-EPMC7556090 | biostudies-literature

FEATURE SCREENING FOR TIME-VARYING COEFFICIENT MODELS WITH ULTRAHIGH DIMENSIONAL LONGITUDINAL DATA.

Project description:Motivated by an empirical analysis of the Childhood Asthma Management Project, CAMP, we introduce a new screening procedure for varying coefficient models with ultrahigh dimensional longitudinal predictor variables. The performance of the proposed procedure is investigated via Monte Carlo simulation. Numerical comparisons indicate that it outperforms existing ones substantially, resulting in significant improvements in explained variability and prediction error. Applying these methods to CAMP, we are able to find a number of potentially important genetic mutations related to lung function, several of which exhibit interesting nonlinear patterns around puberty.

| S-EPMC5019497 | biostudies-literature

Feature selection with interactions in logistic regression models using multivariate synergies for a GWAS application.

Project description:BackgroundGenotype-phenotype association has been one of the long-standing problems in bioinformatics. Identifying both the marginal and epistatic effects among genetic markers, such as Single Nucleotide Polymorphisms (SNPs), has been extensively integrated in Genome-Wide Association Studies (GWAS) to help derive "causal" genetic risk factors and their interactions, which play critical roles in life and disease systems. Identifying "synergistic" interactions with respect to the outcome of interest can help accurate phenotypic prediction and understand the underlying mechanism of system behavior. Many statistical measures for estimating synergistic interactions have been proposed in the literature for such a purpose. However, except for empirical performance, there is still no theoretical analysis on the power and limitation of these synergistic interaction measures.ResultsIn this paper, it is shown that the existing information-theoretic multivariate synergy depends on a small subset of the interaction parameters in the model, sometimes on only one interaction parameter. In addition, an adjusted version of multivariate synergy is proposed as a new measure to estimate the interactive effects, with experiments conducted over both simulated data sets and a real-world GWAS data set to show the effectiveness.ConclusionsWe provide rigorous theoretical analysis and empirical evidence on why the information-theoretic multivariate synergy helps with identifying genetic risk factors via synergistic interactions. We further establish the rigorous sample complexity analysis on detecting interactive effects, confirmed by both simulated and real-world data sets.

| S-EPMC5872388 | biostudies-literature

On Varying-coefficient Independence Screening for High-dimensional Varying-coefficient Models.

Project description:Varying coefficient models have been widely used in longitudinal data analysis, nonlinear time series, survival analysis, and so on. They are natural non-parametric extensions of the classical linear models in many contexts, keeping good interpretability and allowing us to explore the dynamic nature of the model. Recently, penalized estimators have been used for fitting varying-coefficient models for high-dimensional data. In this paper, we propose a new computationally attractive algorithm called IVIS for fitting varying-coefficient models in ultra-high dimensions. The algorithm first fits a gSCAD penalized varying-coefficient model using a subset of covariates selected by a new varying-coefficient independence screening (VIS) technique. The sure screening property is established for VIS. The proposed algorithm then iterates between a greedy conditional VIS step and a gSCAD penalized fitting step. Simulation and a real data analysis demonstrate that IVIS has very competitive performance for moderate sample size and high dimension.

| S-EPMC4251601 | biostudies-literature

A varying-coefficient generalized odds rate model with time-varying exposure: An application to fitness and cardiovascular disease mortality.

Project description:Varying-coefficient models have become a common tool to determine whether and how the association between an exposure and an outcome changes over a continuous measure. These models are complicated when the exposure itself is time-varying and subjected to measurement error. For example, it is well known that longitudinal physical fitness has an impact on cardiovascular disease (CVD) mortality. It is not known, however, how the effect of longitudinal physical fitness on CVD mortality varies with age. In this paper, we propose a varying-coefficient generalized odds rate model that allows flexible estimation of age-modified effects of longitudinal physical fitness on CVD mortality. In our model, the longitudinal physical fitness is measured with error and modeled using a mixed-effects model, and its associated age-varying coefficient function is represented by cubic B-splines. An expectation-maximization algorithm is developed to estimate the parameters in the joint models of longitudinal physical fitness and CVD mortality. A modified pseudoadaptive Gaussian-Hermite quadrature method is adopted to compute the integrals with respect to random effects involved in the E-step. The performance of the proposed method is evaluated through extensive simulation studies and is further illustrated with an application to cohort data from the Aerobic Center Longitudinal Study.

| S-EPMC6736699 | biostudies-literature

Analysis of generalized semiparametric mixed varying-coefficients models for longitudinal data.

Project description:The generalized semiparametric mixed varying-coefficient effects model for longitudinal data can accommodate a variety of link functions and flexibly model different types of covariate effects, including time-constant, time-varying, and covariate-varying effects. The time-varying effects are unspecified functions of time and the covariate-varying effects are nonparametric functions of a possibly time-dependent exposure variable. A semiparametric estimation procedure is developed that uses local linear smoothing and profile weighted least squares, which requires smoothing in the two different and yet connected domains of time and the time-dependent exposure variable. The asymptotic properties of the estimators of both nonparametric and parametric effects are investigated. In addition, hypothesis testing procedures are developed to examine the covariate effects. The finite-sample properties of the proposed estimators and testing procedures are examined through simulations, indicating satisfactory performances. The proposed methods are applied to analyze the ACTG 244 clinical trial to investigate the effects of antiretroviral treatment switching in HIV-infected patients before and after developing the T215Y antiretroviral drug resistance mutation.

| S-EPMC6905629 | biostudies-literature

The coefficient of determination R2 and intra-class correlation coefficient from generalized linear mixed-effects models revisited and expanded.

Project description:The coefficient of determination R2 quantifies the proportion of variance explained by a statistical model and is an important summary statistic of biological interest. However, estimating R2 for generalized linear mixed models (GLMMs) remains challenging. We have previously introduced a version of R2 that we called [Formula: see text] for Poisson and binomial GLMMs, but not for other distributional families. Similarly, we earlier discussed how to estimate intra-class correlation coefficients (ICCs) using Poisson and binomial GLMMs. In this paper, we generalize our methods to all other non-Gaussian distributions, in particular to negative binomial and gamma distributions that are commonly used for modelling biological data. While expanding our approach, we highlight two useful concepts for biologists, Jensen's inequality and the delta method, both of which help us in understanding the properties of GLMMs. Jensen's inequality has important implications for biologically meaningful interpretation of GLMMs, whereas the delta method allows a general derivation of variance associated with non-Gaussian distributions. We also discuss some special considerations for binomial GLMMs with binary or proportion data. We illustrate the implementation of our extension by worked examples from the field of ecology and evolution in the R environment. However, our method can be used across disciplines and regardless of statistical environments.

| S-EPMC5636267 | biostudies-literature

Local Rank Inference for Varying Coefficient Models.

Project description:By allowing the regression coefficients to change with certain covariates, the class of varying coefficient models offers a flexible approach to modeling nonlinearity and interactions between covariates. This paper proposes a novel estimation procedure for the varying coefficient models based on local ranks. The new procedure provides a highly efficient and robust alternative to the local linear least squares method, and can be conveniently implemented using existing R software package. Theoretical analysis and numerical simulations both reveal that the gain of the local rank estimator over the local linear least squares estimator, measured by the asymptotic mean squared error or the asymptotic mean integrated squared error, can be substantial. In the normal error case, the asymptotic relative efficiency for estimating both the coefficient functions and the derivative of the coefficient functions is above 96%; even in the worst case scenarios, the asymptotic relative efficiency has a lower bound 88.96% for estimating the coefficient functions, and a lower bound 89.91% for estimating their derivatives. The new estimator may achieve the nonparametric convergence rate even when the local linear least squares method fails due to infinite random error variance. We establish the large sample theory of the proposed procedure by utilizing results from generalized U-statistics, whose kernel function may depend on the sample size. We also extend a resampling approach, which perturbs the objective function repeatedly, to the generalized U-statistics setting; and demonstrate that it can accurately estimate the asymptotic covariance matrix.

| S-EPMC2908045 | biostudies-literature

BAYESIAN GROUP LASSO FOR NONPARAMETRIC VARYING-COEFFICIENT MODELS WITH APPLICATION TO FUNCTIONAL GENOME-WIDE ASSOCIATION STUDIES.

Project description:Although genome-wide association studies (GWAS) have proven powerful for comprehending the genetic architecture of complex traits, they are challenged by a high dimension of single-nucleotide polymorphisms (SNPs) as predictors, the presence of complex environmental factors, and longitudinal or functional natures of many complex traits or diseases. To address these challenges, we propose a high-dimensional varying-coefficient model for incorporating functional aspects of phenotypic traits into GWAS to formulate a so-called functional GWAS or fGWAS. Bayesian group lasso and the associated MCMC algorithms are developed to identify significant SNPs and estimate how they affect longitudinal traits through time-varying genetic actions. The model is generalized to analyze the genetic control of complex traits using subject-specific sparse longitudinal data. The statistical properties of the new model are investigated through simulation studies. We use the new model to analyze a real GWAS data set from the Framingham Heart Study, leading to the identification of several significant SNPs associated with age-specific changes of body mass index. The fGWAS model, equipped with Bayesian group lassso, will provide a useful tool for genetic and developmental analysis of complex traits or diseases.

| S-EPMC4605444 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data