Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Testing and estimation in marker-set association study using semiparametric quantile regression kernel machine.

ABSTRACT: We consider quantile regression for partially linear models where an outcome of interest is related to covariates and a marker set (e.g., gene or pathway). The covariate effects are modeled parametrically and the marker set effect of multiple loci is modeled using kernel machine. We propose an efficient algorithm to solve the corresponding optimization problem for estimating the effects of covariates and also introduce a powerful test for detecting the overall effect of the marker set. Our test is motivated by traditional score test, and borrows the idea of permutation test. Our estimation and testing procedures are evaluated numerically and applied to assess genetic association of change in fasting homocysteine level using the Vitamin Intervention for Stroke Prevention Trial data.

SUBMITTER: Kong D

PROVIDER: S-EPMC4870165 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Testing and estimation in marker-set association study using semiparametric quantile regression kernel machine.

Kong Dehan D Maity Arnab A Hsu Fang-Chi FC Tzeng Jung-Ying JY

Biometrics 20151117 2

We consider quantile regression for partially linear models where an outcome of interest is related to covariates and a marker set (e.g., gene or pathway). The covariate effects are modeled parametrically and the marker set effect of multiple loci is modeled using kernel machine. We propose an efficient algorithm to solve the corresponding optimization problem for estimating the effects of covariates and also introduce a powerful test for detecting the overall effect of the marker set. Our test ...[more]

PMID: 26575303

Similar Datasets

Reader Reaction: A note on testing and estimation in marker-set association study using semiparametric quantile regression kernel machine.

Project description:Kong et al. (2016, Biometrics 72, 364-371) presented a quantile regression kernel machine (QRKM) test for robust analysis of genetic marker-set association studies. A potential limitation of QRKM is the permutation-based test design may be unscalable for the massive sizes of modern datasets. In this article, we present an alternative strategy for p-value calculation of QRKM, which is capable of speeding up the QRKM testing procedure dramatically while maintaining the same testing performance as QRKM. The effectiveness of our approach is demonstrated via simulation studies.

| S-EPMC5932287 | biostudies-literature

Kernel machine SNP-set testing under multiple candidate kernels.

Project description:Joint testing for the cumulative effect of multiple single-nucleotide polymorphisms grouped on the basis of prior biological knowledge has become a popular and powerful strategy for the analysis of large-scale genetic association studies. The kernel machine (KM)-testing framework is a useful approach that has been proposed for testing associations between multiple genetic variants and many different types of complex traits by comparing pairwise similarity in phenotype between subjects to pairwise similarity in genotype, with similarity in genotype defined via a kernel function. An advantage of the KM framework is its flexibility: choosing different kernel functions allows for different assumptions concerning the underlying model and can allow for improved power. In practice, it is difficult to know which kernel to use a priori because this depends on the unknown underlying trait architecture and selecting the kernel which gives the lowest P-value can lead to inflated type I error. Therefore, we propose practical strategies for KM testing when multiple candidate kernels are present based on constructing composite kernels and based on efficient perturbation procedures. We demonstrate through simulations and real data applications that the procedures protect the type I error rate and can lead to substantially improved power over poor choices of kernels and only modest differences in power vs. using the best candidate kernel.

| S-EPMC3769109 | biostudies-literature

Semiparametric distributed lag quantile regression for modeling time-dependent exposure mixtures.

Project description:Studying time-dependent exposure mixtures has gained increasing attentions in environmental health research. When a scalar outcome is of interest, distributed lag (DL) models have been employed to characterize the exposures effects distributed over time on the mean of final outcome. However, there is a methodological gap on investigating time-dependent exposure mixtures with different quantiles of outcome. In this paper, we introduce semiparametric partial-linear single-index (PLSI) DL quantile regression, which can describe the DL effects of time-dependent exposure mixtures on different quantiles of outcome and identify susceptible periods of exposures. We consider two time-dependent exposure settings: discrete and functional, when exposures are measured in a small number of time points and at dense time grids, respectively. Spline techniques are used to approximate the nonparametric DL function and single-index link function, and a profile estimation algorithm is proposed. Through extensive simulations, we demonstrate the performance and value of our proposed models and inference procedures. We further apply the proposed methods to study the effects of maternal exposures to ambient air pollutants of fine particulate and nitrogen dioxide on birth weight in New York University Children's Health and Environment Study (NYU CHES).

| S-EPMC10718172 | biostudies-literature

MiRKAT: kernel machine regression-based global association tests for the microbiome.

Project description:SummaryDistance-based tests of microbiome beta diversity are an integral part of many microbiome analyses. MiRKAT enables distance-based association testing with a wide variety of outcome types, including continuous, binary, censored time-to-event, multivariate, correlated and high-dimensional outcomes. Omnibus tests allow simultaneous consideration of multiple distance and dissimilarity measures, providing higher power across a range of simulation scenarios. Two measures of effect size, a modified R-squared coefficient and a kernel RV coefficient, are incorporated to allow comparison of effect sizes across multiple kernels.Availability and implementationMiRKAT is available on CRAN as an R package.Supplementary informationSupplementary data are available at Bioinformatics online.

| S-EPMC8495888 | biostudies-literature

Ensemble estimation and variable selection with semiparametric regression models.

Project description:We consider scenarios in which the likelihood function for a semiparametric regression model factors into separate components, with an efficient estimator of the regression parameter available for each component. An optimal weighted combination of the component estimators, named an ensemble estimator, may be employed as an overall estimate of the regression parameter, and may be fully efficient under uncorrelatedness conditions. This approach is useful when the full likelihood function may be difficult to maximize, but the components are easy to maximize. It covers settings where the nuisance parameter may be estimated at different rates in the component likelihoods. As a motivating example we consider proportional hazards regression with prospective doubly censored data, in which the likelihood factors into a current status data likelihood and a left-truncated right-censored data likelihood. Variable selection is important in such regression modelling, but the applicability of existing techniques is unclear in the ensemble approach. We propose ensemble variable selection using the least squares approximation technique on the unpenalized ensemble estimator, followed by ensemble re-estimation under the selected model. The resulting estimator has the oracle property such that the set of nonzero parameters is successfully recovered and the semiparametric efficiency bound is achieved for this parameter set. Simulations show that the proposed method performs well relative to alternative approaches. Analysis of an AIDS cohort study illustrates the practical utility of the method.

| S-EPMC7228544 | biostudies-literature

Semiparametrically efficient estimation in quantile regression of secondary analysis.

Project description:Analysing secondary outcomes is a common practice for case-control studies. Traditional secondary analysis employs either completely parametric models or conditional mean regression models to link the secondary outcome to covariates. In many situations, quantile regression models complement mean-based analyses and provide alternative new insights on the associations of interest. For example, biomedical outcomes are often highly asymmetric, and median regression is more useful in describing the 'central' behaviour than mean regressions. There are also cases where the research interest is to study the high or low quantiles of a population, as they are more likely to be at risk. We approach the secondary quantile regression problem from a semiparametric perspective, allowing the covariate distribution to be completely unspecified. We derive a class of consistent semiparametric estimators and identify the efficient member. The asymptotic properties of the resulting estimators are established. Simulation results and a real data analysis are provided to demonstrate the superior performance of our approach with a comparison with the only existing approach so far in the literature.

| S-EPMC6191046 | biostudies-literature

Testing for Marginal Linear Effects in Quantile Regression.

Project description:This paper develops a new marginal testing procedure to detect the presence of significant predictors associated with the conditional quantiles of a scalar response. The idea is to fit the marginal quantile regression on each predictor one at a time, and then base the test on the t-statistics associated with the most predictive predictors. A resampling method is devised to calibrate this test statistic, which has non-regular limiting behavior due to the selection of the most predictive variables. Asymptotic validity of the procedure is established in a general quantile regression setting in which the marginal quantile regression models can be misspecified. Even though a fixed dimension is assumed to derive the asymptotic results, the proposed test is applicable and computationally feasible for large-dimensional predictors. The method is more flexible than existing marginal screening test methods based on mean regression, and has the added advantage of being robust against outliers in the response. The approach is illustrated using an application to an HIV drug resistance dataset.

| S-EPMC5863930 | biostudies-literature

Sparse kernel machine regression for ordinal outcomes.

Project description:Ordinal outcomes arise frequently in clinical studies when each subject is assigned to a category and the categories have a natural order. Classification rules for ordinal outcomes may be developed with commonly used regression models such as the full continuation ratio (CR) model (fCR), which allows the covariate effects to differ across all continuation ratios, and the CR model with a proportional odds structure (pCR), which assumes the covariate effects to be constant across all continuation ratios. For settings where the covariate effects differ between some continuation ratios but not all, fitting either fCR or pCR may lead to suboptimal prediction performance. In addition, these standard models do not allow for nonlinear covariate effects. In this article, we propose a sparse CR kernel machine (KM) regression method for ordinal outcomes where we use the KM framework to incorporate nonlinearity and impose sparsity on the overall differences between the covariate effects of continuation ratios to control for overfitting. In addition, we provide data driven rule to select an optimal kernel to maximize the prediction accuracy. Simulation results show that our proposed procedures perform well under both linear and nonlinear settings, especially when the true underlying model is in-between fCR and pCR models. We apply our procedures to develop a prediction model for levels of anti-CCP among rheumatoid arthritis patients and demonstrate the advantage of our method over other commonly used methods.

| S-EPMC4609171 | biostudies-literature

Modelling and estimation of nonlinear quantile regression with clustered data.

Project description:In regression applications, the presence of nonlinearity and correlation among observations offer computational challenges not only in traditional settings such as least squares regression, but also (and especially) when the objective function is nonsmooth as in the case of quantile regression. Methods are developed for the modelling and estimation of nonlinear conditional quantile functions when data are clustered within two-level nested designs. The proposed estimation algorithm is a blend of a smoothing algorithm for quantile regression and a second order Laplacian approximation for nonlinear mixed models. This optimization approach has the appealing advantage of reducing the original nonsmooth problem to an approximated L 2 problem. While the estimation algorithm is iterative, the objective function to be optimized has a simple analytic form. The proposed methods are assessed through a simulation study and two applications, one in pharmacokinetics and one related to growth curve modelling in agriculture.

| S-EPMC6663105 | biostudies-literature

Quantile association regression on bivariate survival data.

Project description:The association between two event times is of scientific importance in various fields. Due to population heterogeneity, it is desirable to examine the degree to which local association depends on different characteristics of the population. Here we adopt a novel quantile-based local association measure and propose a conditional quantile association regression model to allow covariate effects on local association of two survival times. Estimating equations for the quantile association coefficients are constructed based on the relationship between this quantile association measure and the conditional copula. Asymptotic properties for the resulting estimators are rigorously derived, and induced smoothing is used to obtain the covariance matrix. Through simulations we demonstrate the good practical performance of the proposed inference procedures. An application to age-related macular degeneration (AMD) data reals interesting varying effects of the baseline AMD severity score on the local association between two AMD progression times.

| S-EPMC8552531 | 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