We present generalized additive latent and mixed models (GALAMMs) for analysis of clustered data with responses and latent variables depending smoothly on observed variables. A scalable maximum likelihood estimation algorithm is proposed, utilizing the Laplace approximation, sparse matrix computation, and automatic differentiation. Mixed response types, heteroscedasticity, and crossed random effects are naturally incorporated into the framework. The models developed were motivated by applications in cognitive neuroscience, and two case studies are presented. First, we show how GALAMMs can jointly model the complex lifespan trajectories of episodic memory, working memory, and speed/executive function, measured by the California Verbal Learning Test (CVLT), digit span tests, and Stroop tests, respectively. Next, we study the effect of socioeconomic status on brain structure, using data on education and income together with hippocampal volumes estimated by magnetic resonance imaging. By combining semiparametric estimation with latent variable modeling, GALAMMs allow a more realistic representation of how brain and cognition vary across the lifespan, while simultaneously estimating latent traits from measured items. Simulation experiments suggest that model estimates are accurate even with moderate sample sizes.
Bifurcating Markov chains (BMC) are Markov chains indexed by a full binary tree representing the evolution of a trait along a population where each individual has two children. We provide a central limit theorem for general additive functionals of BMC, and prove the existence of three regimes. This corresponds to a competition between the reproducing rate (each individual has two children) and the ergodicity rate for the evolution of the trait. This is in contrast with the work of Guyon (2007), where the considered additive functionals are sums of martingale increments, and only one regime app…
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…
Rooted in genetics, human complex diseases are largely influenced by environmental factors. Existing literature has shown the power of integrative gene-environment interaction analysis by considering the joint effect of environmental mixtures on a disease risk. In this work, we propose a functional varying index coefficient model for longitudinal measurements of a phenotypic trait together with multiple environmental variables, and assess how the genetic effects on a longitudinal disease trait are nonlinearly modified by a mixture of environmental influences. We derive an estimation procedure …
Additive models are flexible regression tools that handle linear as well as nonlinear terms. The latter are typically modelled via smoothing splines. Additive mixed models extend additive models to include random terms when the data are sampled according to cluster designs (e.g., longitudinal). These models find applications in the study of phenomena like growth, certain disease mechanisms and energy consumption in humans, when repeated measurements are available. In this paper, we propose a novel additive mixed model for quantile regression. Our methods are motivated by an application to phys…
This work deals with the analysis of longitudinal ordinal responses. The novelty of the proposed approach is in modeling simultaneously the temporal dynamics of a latent trait of interest, measured via the observed ordinal responses, and the answering behaviors influenced by response styles, through hidden Markov models (HMMs) with two latent components. This approach enables the modeling of (i) the substantive latent trait, controlling for response styles; (ii) the change over time of latent trait and answering behavior, allowing also dependence on individual characteristics. For the proposed…
In many longitudinal studies, the covariate and response are often intermittently observed at irregular, mismatched and subject-specific times. How to deal with such data when covariate and response are observed asynchronously is an often raised problem. Bayesian Additive Regression Trees(BART) is a Bayesian non-Parametric approach which has been shown to be competitive with the best modern predictive methods such as random forest and boosted decision trees. The sum of trees structure combined with a Bayesian inferential framework provide a accurate and robust statistic method. BART variant so…
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…
In light of recent work studying massive functional/longitudinal data, such as the resulting data from the COVID-19 pandemic, we propose a novel functional/longitudinal data model which is a combination of the popular varying coefficient (VC) model and additive model. We call it Semi-VCAM in which the response could be a functional/longitudinal variable, and the explanatory variables could be a mixture of functional/longitudinal and scalar variables. Notably some of the scalar variables could be categorical variables as well. The Semi-VCAM simultaneously allows for both substantial flexibility…
In epidemiological and clinical studies, identifying patients' phenotypes based on longitudinal profiles is critical to understanding the disease's developmental patterns. The current study was motivated by data from a Canadian birth cohort study, the CHILD Cohort Study. Our goal was to use multiple longitudinal respiratory traits to cluster the participants into subgroups with similar longitudinal respiratory profiles in order to identify clinically relevant disease phenotypes. To appropriately account for distinct structures and types of these longitudinal markers, we proposed a novel joint …
Observational longitudinal data on treatments and covariates are increasingly used to investigate treatment effects, but are often subject to time-dependent confounding. Marginal structural models (MSMs), estimated using inverse probability of treatment weighting or the g-formula, are popular for handling this problem. With increasing development of advanced causal inference methods, it is important to be able to assess their performance in different scenarios to guide their application. Simulation studies are a key tool for this, but their use to evaluate causal inference methods has been lim…
We propose an extensive framework for additive regression models for correlated functional responses, allowing for multiple partially nested or crossed functional random effects with flexible correlation structures for, e.g., spatial, temporal, or longitudinal functional data. Additionally, our framework includes linear and nonlinear effects of functional and scalar covariates that may vary smoothly over the index of the functional response. It accommodates densely or sparsely observed functional responses and predictors which may be observed with additional error and includes both spline-base…
The joint modeling of longitudinal and time-to-event data is an important tool of growing popularity to gain insights into the association between a biomarker and an event process. We develop a general framework of flexible additive joint models that allows the specification of a variety of effects, such as smooth nonlinear, time-varying and random effects, in the longitudinal and survival parts of the models. Our extensions are motivated by the investigation of the relationship between fluctuating disease-specific markers, in this case autoantibodies, and the progression to the autoimmune dis…
Joint models of longitudinal and survival data have become an important tool for modeling associations between longitudinal biomarkers and event processes. The association between marker and log-hazard is assumed to be linear in existing shared random effects models, with this assumption usually remaining unchecked. We present an extended framework of flexible additive joint models that allows the estimation of nonlinear, covariate specific associations by making use of Bayesian P-splines. Our joint models are estimated in a Bayesian framework using structured additive predictors for all model…
We present a coherent Bayesian framework for selection of the most likely model from the five genetic models (genotypic, additive, dominant, co-dominant, and recessive) commonly used in genetic association studies. The approach uses a polynomial parameterization of genetic data to simultaneously fit the five models and save computations. We provide a closed-form expression of the marginal likelihood for normally distributed data, and evaluate the performance of the proposed method and existing method through simulated and real genome-wide data sets.
We propose a comprehensive framework for additive regression models for non-Gaussian functional responses, allowing for multiple (partially) nested or crossed functional random effects with flexible correlation structures for, e.g., spatial, temporal, or longitudinal functional data as well as linear and nonlinear effects of functional and scalar covariates that may vary smoothly over the index of the functional response. Our implementation handles functional responses from any exponential family distribution as well as many others like Beta- or scaled non-central $t$-distributions. Developmen…
We propose a versatile and computationally efficient estimating equation method for a class of hierarchical multiplicative generalized linear mixed models with additive dispersion components, based on explicit modelling of the covariance structure. The class combines longitudinal and random effects models and retains a marginal as well as a conditional interpretation. The estimation procedure combines that of generalized estimating equations for the regression with residual maximum likelihood estimation for the association parameters. This avoids the multidimensional integral of the convention…
The explosion of data throughout the biomedical sciences provides unprecedented opportunities to learn about the dynamics of evolution and disease progression, but harnessing these large and diverse datasets remains challenging. Here, we describe a highly generalisable statistical platform to infer the dynamic pathways by which many, potentially interacting, discrete traits are acquired or lost over time in biomedical systems. The platform uses HyperTraPS (hypercubic transition path sampling) to learn progression pathways from cross-sectional, longitudinal, or phylogenetically-linked data with…
Analyses of biomedical studies often necessitate modeling longitudinal causal effects. The current focus on personalized medicine and effect heterogeneity makes this task even more challenging. Towards this end, structural nested mean models (SNMMs) are fundamental tools for studying heterogeneous treatment effects in longitudinal studies. However, when outcomes are binary, current methods for estimating multiplicative and additive SNMM parameters suffer from variation dependence between the causal parameters and the non-causal nuisance parameters. This leads to a series of difficulties in int…
Regression modelling of spatiotemporal extreme U.S. wildfires via partially-interpretable neural networks
School of Mathematics, University of Edinburgh（爱丁堡大学数学学院）；Statistics Program, Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division, King Abdullah University of Science and Technology (KAUST)（阿卜杜拉国王科技大学计算机、电气与数学科学与工程（CEMSE）分部统计项目）
Penalized variable selection for high dimensional longitudinal data has received much attention as accounting for the correlation among repeated measurements and 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 t…
We propose a fast bivariate smoothing approach for symmetric surfaces that has a wide range of applications. We show how it can be applied to estimate the covariance function in longitudinal data as well as multiple additive covariances in functional data with complex correlation structures. Our symmetric smoother can handle (possibly noisy) data sampled on a common, dense grid as well as irregularly or sparsely sampled data. Estimation is based on bivariate penalized spline smoothing using a mixed model representation and the symmetry is used to reduce computation time compared to the usual n…
A Bayesian semi-parametric approach to causal mediation for longitudinal mediators and time-to-event outcomes with application to a cardiovascular disease cohort study
We present a flexible Bayesian semiparametric mixed model for longitudinal data analysis in the presence of potentially high-dimensional categorical covariates. Building on a novel hidden Markov tensor decomposition technique, our proposed method allows the fixed effects components to vary between dependent random partitions of the covariate space at different time points. The mechanism not only allows different sets of covariates to be included in the model at different time points but also allows the selected predictors' influences to vary flexibly over time. Smooth time-varying additive ran…
We discuss causal mediation analyses for survival data and propose a new approach based on the additive hazards model. The emphasis is on a dynamic point of view, that is, understanding how the direct and indirect effects develop over time. Hence, importantly, we allow for a time varying mediator. To define direct and indirect effects in such a longitudinal survival setting we take an interventional approach (Didelez (2018)) where treatment is separated into one aspect affecting the mediator and a different aspect affecting survival. In general, this leads to a version of the non-parametric g-…
Marginal structural models (MSMs) allow for causal analysis of longitudinal data. The MSMs were originally developed as discrete time models. Recently, continuous-time MSMs were presented as a conceptually appealing alternative for survival analysis. In applied analyses, it is often assumed that the theoretical treatment weights are known, but these weights are usually unknown and must be estimated from the data. Here we provide a sufficient condition for a class of continuous-time MSMs to be consistent even when the weights are estimated, and we show how additive hazard models can be used to …
Longitudinal study designs are indispensable for studying disease progression. Inferring covariate effects from longitudinal data, however, requires interpretable methods that can model complicated covariance structures and detect nonlinear effects of both categorical and continuous covariates, as well as their interactions. Detecting disease effects is hindered by the fact that they often occur rapidly near the disease initiation time, and this time point cannot be exactly observed. An additional challenge is that the effect magnitude can be heterogeneous over the subjects. We present lgpr, a…
Models for dependent data are distinguished by their targets of inference. Marginal models are useful when interest lies in quantifying associations averaged across a population of clusters. When the functional form of a covariate-outcome association is unknown, flexible regression methods are needed to allow for potentially non-linear relationships. We propose a novel marginal additive model (MAM) for modelling cluster-correlated data with non-linear population-averaged associations. The proposed MAM is a unified framework for estimation and uncertainty quantification of a marginal mean model…
