Standard logistic regression analysis of case-control data has low power to detect gene-environment interactions, but until recently it was the only method that could be used on complex polygenic data for which parametric distributional models are not feasible. Under the assumption of gene-environment independence in the underlying population, Stalder et al. (2017, Biometrika, 104, 801-812) developed a retrospective method that treats both genetic and environmental variables nonparametrically. However, the mathematical symmetry of genetic and environmental variables is overlooked. We propose an improvement to the method of Stalder et al. (2017) that increases the efficiency of the estimates with no additional assumptions and modest computational cost. This improvement is achieved by treating the genetic and environmental variables symmetrically to generate two sets of parameter estimates that are combined to generate a more efficient estimate. We employ a semiparametric framework to develop the asymptotic theory of the estimator, show its asymptotic efficiency gain, and evaluate its performance via simulation studies. The method is illustrated using data from a case-control study of breast cancer.
We consider a semiparametric generalized linear model and study estimation of both marginal and quantile effects in this model. We propose an approximate maximum likelihood estimator, and rigorously establish the consistency, the asymptotic normality, and the semiparametric efficiency of our method in both the marginal effect and the quantile effect estimation. Simulation studies are conducted to illustrate the finite sample performance, and we apply the new tool to analyze a Swiss non-labor income data and discover a new interesting predictor.
A biological pathway represents a set of genes that serves a particular cellular or a physiological function. The genes within the same pathway are expected to function together and hence may interact with each other. It is also known that many genes, and so pathways, interact with other environmental variables. However, no formal procedure has yet been developed to evaluate the pathway-environment interaction. In this article, we propose a semiparametric method to model the pathway-environment interaction. The method connects a least square kernel machine and a semiparametric mixed effects mo…
We study semiparametric time series models with innovations following a log-concave distribution. We propose a general maximum likelihood framework which allows us to estimate simultaneously the parameters of the model and the density of the innovations. This framework can be easily adapted to many well-known models, including ARMA, GARCH and ARMA-GARCH. Furthermore, we show that the estimator under our new framework is consistent in both ARMA and ARMA-GARCH settings. We demonstrate its finite sample performance via a thorough simulation study and apply it to model the daily log-return of FTSE…
This research is motivated by discovering and underpinning genetic causes for the progression of a bilateral eye disease, Age-related Macular Degeneration (AMD), of which the primary outcomes, progression times to late-AMD, are bivariate and interval-censored due to intermittent assessment times. We propose a novel class of copula-based semiparametric transformation models for bivariate data under general interval censoring, which includes the case 1 interval censoring (current status data) and case 2 interval censoring. Specifically, the joint likelihood is modeled through a two-parameter Arc…
A Semiparametric Functional Generalized Linear Model for Multi-Population Data
Sauder School of Business, University of British Columbia（不列颠哥伦比亚大学 Sauder 商学院）；Columbia University（哥伦比亚大学）；Department of Statistics and Actuarial Science, Simon Fraser University（西蒙菲莎大学统计与精算科学系）
Traditionally, the Dirichlet-multinomial distribution has been recognized as a key model for contingency tables generated by cluster sampling schemes. There are, however, other possible distributions appropriate for these contingency tables. This paper introduces new test-statistics capable to test log-linear modeling hypotheses with no distributional specification, when the individuals of the clusters are possibly homogeneously correlated. The estimator for the intracluster correlation coefficient proposed in Alonso-Revenga et al. (2016), valid for different cluster sizes, plays a crucial rol…
In fitting a mixture of linear regression models, normal assumption is traditionally used to model the error and then regression parameters are estimated by the maximum likelihood estimators (MLE). This procedure is not valid if the normal assumption is violated. To relax the normal assumption on the error distribution hence reduce the modeling bias, we propose semiparametric mixture of linear regression models with unspecified error distributions. We establish a more general identifiability result under weaker conditions than existing results, construct a class of new estimators, and establis…
When facing multivariate covariates, general semiparametric regression techniques come at hand to propose flexible models that are unexposed to the curse of dimensionality. In this work a semiparametric copula-based estimator for conditional quantiles is investigated for complete or right-censored data. In spirit, the methodology is extending the recent work of Noh et al. (2013) and Noh et al. (2015), as the main idea consists in appropriately defining the quantile regression in terms of a multivariate copula and marginal distributions. Prior estimation of the latter and simple plug-in lead to…
Non-ignorable dropout is common in studies with long follow-up time, and it can bias study results unless handled carefully. A double-sampling design allocates additional resources to pursue a subsample of the dropouts and find out their outcomes, which can address potential biases due to non-ignorable dropout. It is desirable to construct semiparametric estimators for the double-sampling design because of their robustness properties. However, obtaining such semiparametric estimators remains a challenge due to the requirement of the analytic form of the efficient influence function (EIF), the …
A theorem of McCann shows that for any two absolutely continuous probability measures on R^d there exists a monotone transformation sending one probability measure to the other. A consequence of this theorem, relevant to statistics, is that density estimation can be recast in terms of transformations. In particular, one can fix any absolutely continuous probability measure, call it P, and then reparameterize the whole class of absolutely continuous probability measures as monotone transformations from P. In this paper we utilize this reparameterization of densities, as monotone transformations…
Consider semiparametric estimation where a doubly robust estimating function for a low-dimensional parameter is available, depending on two working models. With high-dimensional data, we develop regularized calibrated estimation as a general method for estimating the parameters in the two working models, such that valid Wald confidence intervals can be obtained for the parameter of interest under suitable sparsity conditions if either of the two working models is correctly specified. We propose a computationally tractable two-step algorithm and provide rigorous theoretical analysis which justi…
This paper considers a semiparametric generalized autoregressive conditional heteroskedasticity (S-GARCH) model. For this model, we first estimate the time-varying long run component for unconditional variance by the kernel estimator, and then estimate the non-time-varying parameters in GARCH-type short run component by the quasi maximum likelihood estimator (QMLE). We show that the QMLE is asymptotically normal with the parametric convergence rate. Next, we construct a Lagrange multiplier test for linear parameter constraint and a portmanteau test for model checking, and obtain their asymptot…
Motivated by studies in biological sciences to detect differentially expressed genes, a semiparametric two-component mixture model with one known component is being studied in this paper. Assuming the density of the unknown component to be log-concave, which contains a very broad family of densities, we develop a semiparametric maximum likelihood estimator and propose an EM algorithm to compute it. Our new estimation method finds the mixing proportions and the distribution of the unknown component simultaneously. We establish the identifiability of the proposed semiparametric mixture model and…
In this paper, we propose new semiparametric procedures for making inference on linear functionals and their functions of two semicontinuous populations. The distribution of each population is usually characterized by a mixture of a discrete point mass at zero and a continuous skewed positive component, and hence such distribution is semicontinuous in the nature. To utilize the information from both populations, we model the positive components of the two mixture distributions via a semiparametric density ratio model. Under this model setup, we construct the maximum empirical likelihood estima…
This paper considers a wide family of semiparametric repeated measures regression models, in which the main interest is on estimating population-level quantities such as mean, variance, probabilities etc. Examples of our framework include generalized linear models for clustered/longitudinal data, among many others. We derive plug-in kernel-based estimators of the population level quantities and derive their asymptotic distribution. An example involving estimation of the survival function of hemoglobin measures in the Kenya hemoglobin study data is presented to demonstrate our methodology.
We propose a new class of semiparametric regression models of mean residual life for censored outcome data. The models, which enable us to estimate the expected remaining survival time and generalize commonly used mean residual life models, also conduct covariate dimension reduction. Using the geometric approaches in semiparametrics literature and the martingale properties with survival data, we propose a flexible inference procedure that relaxes the parametric assumptions on the dependence of mean residual life on covariates and how long a patient has lived. We show that the estimators for th…
In this article, we consider an imputation method to handle missing response values based on semiparametric quantile regression estimation. In the proposed method, the missing response values are generated using the estimated conditional quantile regression function at given values of covariates. We adopt the generalized method of moments for estimation of parameters defined through a general estimation equation. We demonstrate that the proposed estimator, which combines both semiparametric quantile regression imputation and generalized method of moments, has competitive edge against some of t…
Analyzing polytomous response from a complex survey scheme, like stratified or cluster sampling is very crucial in several socio-economics applications. We present a class of minimum quasi weighted density power divergence estimators for the polytomous logistic regression model with such a complex survey. This family of semiparametric estimators is a robust generalization of the maximum quasi weighted likelihood estimator exploiting the advantages of the popular density power divergence measure. Accordingly robust estimators for the design effects are also derived. Robust testing of general li…
There is a difficulty in finding an estimate of variance of the profile likelihood estimator in the joint model of longitudinal and survival data. We solve the difficulty by introducing the ``statistical generalized derivative''. The derivative is used to show the asymptotic normality of the estimator without assuming the second derivative of the density function in the model exists.
Consider $M$-estimation in a semiparametric model that is characterized by a Euclidean parameter of interest and an infinite-dimensional nuisance parameter. As a general purpose approach to statistical inferences, the bootstrap has found wide applications in semiparametric $M$-estimation and, because of its simplicity, provides an attractive alternative to the inference approach based on the asymptotic distribution theory. The purpose of this paper is to provide theoretical justifications for the use of bootstrap as a semiparametric inferential tool. We show that, under general conditions, the…
Interval-censored multi-state data arise in many studies of chronic diseases, where the health status of a subject can be characterized by a finite number of disease states and the transition between any two states is only known to occur over a broad time interval. We formulate the effects of potentially time-dependent covariates on multi-state processes through semiparametric proportional intensity models with random effects. We adopt nonparametric maximum likelihood estimation (NPMLE) under general interval censoring and develop a stable expectation-maximization (EM) algorithm. We show that …
In this work we present a simple estimation procedure for a general frailty model for analysis of prospective correlated failure times. Earlier work showed this method to perform well in a simulation study. Here we provide rigorous large-sample theory for the proposed estimators of both the regression coefficient vector and the dependence parameter, including consistent variance estimators.
Case-cohort design, an outcome-dependent sampling design for censored survival data, is increasingly used in biomedical research. The development of asymptotic theory for a case-cohort design in the current literature primarily relies on counting process stochastic integrals. Such an approach, however, is rather limited and lacks theoretical justification for outcome-dependent weighted methods due to non-predictability. Instead of stochastic integrals, we derive asymptotic properties for case-cohort studies based on a general Z-estimation theory for semiparametric models with bundled parameter…
This paper introduces and analyzes a stochastic search method for parameter estimation in linear regression models in the spirit of Beran and Millar (1987). The idea is to generate a random finite subset of a parameter space which will automatically contain points which are very close to an unknown true parameter. The motivation for this procedure comes from recent work of Duembgen, Samworth and Schuhmacher (2011) on regression models with log-concave error distributions.
This paper addresses the problem of semiparametric efficiency bounds for conditional moment restriction models with different conditioning variables. We characterize such an efficiency bound, that in general is not explicit, as a limit of explicit efficiency bounds for a decreasing sequence of unconditional (marginal) moment restriction models. An iterative procedure for approximating the efficient score when this is not explicit is provided. Our theoretical results complete and extend existing results in the literature, provide new insight for the theory of semiparametric efficiency bounds li…
A Bernstein-von Mises theorem is derived for general semiparametric functionals. The result is applied to a variety of semiparametric problems in i.i.d. and non-i.i.d. situations. In particular, new tools are developed to handle semiparametric bias, in particular for nonlinear functionals and in cases where regularity is possibly low. Examples include the squared $L^2$-norm in Gaussian white noise, nonlinear functionals in density estimation, as well as functionals in autoregressive models. For density estimation, a systematic study of BvM results for two important classes of priors is provide…
Logistic regression with unknown sizes has many important applications in biological and medical sciences. All models about this problem in the literature are parametric ones. A semiparametric regression model is proposed. This model incorporates overdispersion due to the variation of sizes, and allows general dose-response relations. An Expectation Conditional Maximization algorithm is provided to maximize the log likelihood. The bootstrap method can be used to construct confidence intervals for regression coefficients. Simulation is performed to study the behavior of the proposed model. Two …
The bootstrap variance estimate is widely used in semiparametric inferences. However, its theoretical validity is a well known open problem. In this paper, we provide a {\em first} theoretical study on the bootstrap moment estimates in semiparametric models. Specifically, we establish the bootstrap moment consistency of the Euclidean parameter which immediately implies the consistency of $t$-type bootstrap confidence set. It is worth pointing out that the only additional cost to achieve the bootstrap moment consistency in contrast with the distribution consistency is to simply strengthen the $…
In this paper, we are concerned with how to select significant variables in semiparametric modeling. Variable selection for semiparametric regression models consists of two components: model selection for nonparametric components and selection of significant variables for the parametric portion. Thus, semiparametric variable selection is much more challenging than parametric variable selection (e.g., linear and generalized linear models) because traditional variable selection procedures including stepwise regression and the best subset selection now require separate model selection for the non…
A common practice in obtaining a semiparametric efficient estimate is through iteratively maximizing the (penalized) log-likelihood w.r.t. its Euclidean parameter and functional nuisance parameter via Newton-Raphson algorithm. The purpose of this paper is to provide a formula in calculating the minimal number of iterations $k^\ast$ needed to produce an efficient estimate $\hatθ_n^{(k^\ast)}$ from a theoretical point of view. We discover that (a) $k^\ast$ depends on the convergence rates of the initial estimate and nuisance estimate; (b) more than $k^\ast$ iterations, i.e., $k$, will only impro…
This paper considers an estimation of semiparametric functional (varying)-coefficient quantile regression with spatial data. A general robust framework is developed that treats quantile regression for spatial data in a natural semiparametric way. The local M-estimators of the unknown functional-coefficient functions are proposed by using local linear approximation, and their asymptotic distributions are then established under weak spatial mixing conditions allowing the data processes to be either stationary or nonstationary with spatial trends. Application to a soil data set is demonstrated wi…
Penetrance, which plays a key role in genetic research, is defined as the proportion of individuals with the genetic variants (i.e., {genotype}) that cause a particular trait and who have clinical symptoms of the trait (i.e., {phenotype}). We propose a Bayesian semiparametric approach to estimate the cancer-specific age-at-onset penetrance in the presence of the competing risk of multiple cancers. We employ a Bayesian semiparametric competing risk model to model the duration until individuals in a high-risk group develop different cancers, and accommodate family data using family-wise likeliho…
In this paper we propose a generalization of a class of Gaussian Semiparametric Estimators (GSE) of the fractional differencing parameter for long-range dependent multivariate time series. We generalize a known GSE-type estimator by introducing some modifications at the objective function level regarding the process' spectral density matrix estimator. We study large sample properties of the estimator without assuming Gaussianity as well as hypothesis testing. The class of models considered here satisfies simple conditions on the spectral density function, restricted to a small neighborhood of …
There are many interesting and widely used estimators of a functional with finite semiparametric variance bound that depend on nonparametric estimators of nuisance functions. We use cross-fitting (i.e. sample splitting) to construct novel estimators with fast remainder rates. We give cross-fit doubly robust estimators that use separate subsamples to estimate different nuisance functions. We obtain general, precise results for regression spline estimation of average linear functionals of conditional expectations with a finite semiparametric variance bound. We show that a cross-fit doubly robust…
This paper revisits the classical inference results for profile quasi maximum likelihood estimators (profile MLE) in the semiparametric estimation problem. We mainly focus on two prominent theorems: the Wilks phenomenon and Fisher expansion for the profile MLE are stated in a new fashion allowing finite samples and model misspecification. The method of study is also essentially different from the usual analysis of the semiparametric problem based on the notion of the hardest parametric submodel. Instead we derive finite sample deviation bounds for the linear approximation error for the gradien…
We consider efficient estimation of the Euclidean parameters in a generalized partially linear additive models for longitudinal/clustered data when multiple covariates need to be modeled nonparametrically, and propose an estimation procedure based on a spline approximation of the nonparametric part of the model and the generalized estimating equations (GEE). Although the model in consideration is natural and useful in many practical applications, the literature on this model is very limited because of challenges in dealing with dependent data for nonparametric additive models. We show that the…
We propose a new class of semiparametric exponential family graphical models for the analysis of high dimensional mixed data. Different from the existing mixed graphical models, we allow the nodewise conditional distributions to be semiparametric generalized linear models with unspecified base measure functions. Thus, one advantage of our method is that it is unnecessary to specify the type of each node and the method is more convenient to apply in practice. Under the proposed model, we consider both problems of parameter estimation and hypothesis testing in high dimensions. In particular, we …
In this article, we study a partially linear single-index model for longitudinal data under a general framework which includes both the sparse and dense longitudinal data cases. A semiparametric estimation method based on a combination of the local linear smoothing and generalized estimation equations (GEE) is introduced to estimate the two parameter vectors as well as the unknown link function. Under some mild conditions, we derive the asymptotic properties of the proposed parametric and nonparametric estimators in different scenarios, from which we find that the convergence rates and asympto…
DNA-SE: Towards Deep Neural-Nets Assisted Semiparametric Estimation
The University of Hong Kong（香港大学）；Shanghai Jiao Tong University（上海交通大学）；Institute of Natural Sciences（自然科学研究院）；SJTU-Yale Joint Center for Biostatistics and Data Science（上海交通大学-耶鲁大学生物统计学与数据科学联合中心）；Columbia University（哥伦比亚大学）
This paper is first devoted to study an adaptive wavelet based estimator of the long memory parameter for linear processes in a general semi-parametric frame. This is an extension of Bardet {\it et al.} (2008) which only concerned Gaussian processes. Moreover, the definition of the long memory parameter estimator is modified and asymptotic results are improved even in the Gaussian case. Finally an adaptive goodness-of-fit test is also built and easy to be employed: it is a chi-square type test. Simulations confirm the interesting properties of consistency and robustness of the adaptive estimat…
In this paper, we mainly discuss the cure model with survival data. Different from the usual survival data with right-censoring, we incorporate the features of left-truncation and measurement error in covariates. Generally speaking, left-truncation causes a biased sample in survival analysis; measurement error in covariates may incur a tremendous bias if we do not deal with it properly. To deal with these challenges, we propose a flexible way to analyze left-truncated survival data and correct measurement error in covariates. The theoretical results are also established in this paper.
We disucss a statistical estimation problem of an optimal dividend barrier when the surplus process follows a Lévy insurance risk process. The optimal dividend barrier is defined as the level of the barrier that maximizes the expectation of the present value of all dividend payments until ruin. In this paper, an estimatior of the expected present value of all dividend payments is defined based on ``quasi-process'' in which sample paths are generated by shuffling increments of a sample path of the Lévy insurance risk process. The consistency of the optimal dividend barrier estimator is shown. M…
Polygenic risk scores (PRS) have recently received much attention for genetics risk prediction. While successful for the Caucasian population, the PRS based on the minority population suffer from small sample sizes, high dimensionality and low signal-to-noise ratios, exacerbating already severe health disparities. Due to population heterogeneity, direct trans-ethnic prediction by utilizing the Caucasian model for the minority population also has limited performance. In addition, due to data privacy, the individual genotype data is not accessible for either the Caucasian population or the minor…
We develop algorithms for performing semiparametric regression analysis in real time, with data processed as it is collected and made immediately available via modern telecommunications technologies. Our definition of semiparametric regression is quite broad and includes, as special cases, generalized linear mixed models, generalized additive models, geostatistical models, wavelet nonparametric regression models and their various combinations. Fast updating of regression fits is achieved by couching semiparametric regression into a Bayesian hierarchical model or, equivalently, graphical model …
Fast variational approximate algorithms are developed for Bayesian semiparametric regression when the response variable is a count, i.e. a non-negative integer. We treat both the Poisson and Negative Binomial families as models for the response variable. Our approach utilizes recently developed methodology known as non-conjugate variational message passing. For concreteness, we focus on generalized additive mixed models, although our variational approximation approach extends to a wide class of semiparametric regression models such as those containing interactions and elaborate random effect s…
We express the mean and variance terms in a double exponential regression model as additive functions of the predictors and use Bayesian variable selection to determine which predictors enter the model, and whether they enter linearly or flexibly. When the variance term is null we obtain a generalized additive model, which becomes a generalized linear model if the predictors enter the mean linearly. The model is estimated using Markov chain Monte Carlo simulation and the methodology is illustrated using real and simulated data sets.
Semiparametric forecasting and filtering are introduced as a method of addressing model errors arising from unresolved physical phenomena. While traditional parametric models are able to learn high-dimensional systems from small data sets, their rigid parametric structure makes them vulnerable to model error. On the other hand, nonparametric models have a very flexible structure, but they suffer from the curse-of-dimensionality and are not practical for high-dimensional systems. The semiparametric approach loosens the structure of a parametric model by fitting a data-driven nonparametric model…
Time-series data in population health and epidemiology often involve non-Gaussian responses. In this note, we propose a semiparametric generalized linear models framework for time-series data that does not require specification of a working conditional response distribution for the data. Instead, the underlying response distribution is treated as an infinite-dimensional parameter which is estimated simultaneously with the usual finite-dimensional parameters via a maximum empirical likelihood approach. A general consistency result for the resulting estimators is given. Simulations suggest that …
In this paper, we propose a general subgroup analysis framework based on semiparametric additive mixed effect models in longitudinal analysis, which can identify subgroups on each covariate and estimate the corresponding regression functions simultaneously. In addition, the proposed procedure is applicable for both balanced and unbalanced longitudinal data. A backfitting combined with k-means algorithm is developed to estimate each semiparametric additive component across subgroups and detect subgroup structure on each covariate respectively. The actual number of groups is estimated by minimiz…
We consider identification and estimation with an outcome missing not at random (MNAR). We study an identification strategy based on a so-called shadow variable. A shadow variable is assumed to be correlated with the outcome, but independent of the missingness process conditional on the outcome and fully observed covariates. We describe a general condition for nonparametric identification of the full data law under MNAR using a valid shadow variable. Our condition is satisfied by many commonly-used models; moreover, it is imposed on the complete cases, and therefore has testable implications w…
Disease subtype identification (clustering) is an important problem in biomedical research. Gene expression profiles are commonly utilized to infer disease subtypes, which often lead to biologically meaningful insights into disease. Despite many successes, existing clustering methods may not perform well when genes are highly correlated and many uninformative genes are included for clustering due to the high dimensionality. In this article, we introduce a novel subtype identification method in the Bayesian setting based on gene expression profiles. This method, called BCSub, adopts an innovati…
