On Multiply Robust Mendelian Randomization (MR2) With Many Invalid Genetic Instruments

Mendelian randomization (MR) is a popular instrumental variable (IV) approach, in which genetic markers are used as IVs. In order to improve efficiency, multiple markers are routinely used in MR analyses, leading to concerns about bias due to possible violation of IV exclusion restriction of no direct effect of any IV on the outcome other than through the exposure in view. To address this concern, we introduce a new class of Multiply Robust MR (MR2) estimators that are guaranteed to remain consistent for the causal effect of interest provided that at least one genetic marker is a valid IV without necessarily knowing which IVs are invalid. We show that the proposed MR2 estimators are a special case of a more general class of estimators that remain consistent provided that a set of at least k† out of K candidate instrumental variables are valid, for k† ≤ K set by the analyst ex ante, without necessarily knowing which IVs are invalid. We provide formal semiparametric theory supporting our results, and characterize the semiparametric efficiency bound for the exposure causal effect which cannot be improved upon by any regular estimator with our favorable robustness property. We conduct extensive simulation studies and apply our methods to a large-scale analysis of UK Biobank data, demonstrating the superior empirical performance of MR2 compared to competing MR methods.

A unified framework for efficient estimation of general treatment models

This paper presents a weighted optimization framework that unifies the binary, multivalued, and continuous treatment—as well as mixture of discrete and continuous treatment—under a unconfounded treatment assignment. With a general loss function, the framework includes the average, quantile, and asymmetric least squares causal effect of treatment as special cases. For this general framework, we first derive the semiparametric efficiency bound for the causal effect of treatment, extending the existing bound results to a wider class of models. We then propose a generalized optimization estimator for the causal effect with weights estimated by solving an expanding set of equations. Under some sufficient conditions, we establish the consistency and asymptotic normality of the proposed estimator of the causal effect and show that the estimator attains the semiparametric efficiency bound, thereby extending the existing literature on efficient estimation of causal effect to a wider class of applications. Finally, we discuss estimation of some causal effect functionals such as the treatment effect curve and the average outcome. To evaluate the finite sample performance of the proposed procedure, we conduct a small‐scale simulation study and find that the proposed estimation has practical value. In an empirical application, we detect a significant causal effect of political advertisements on campaign contributions in the binary treatment model, but not in the continuous treatment model.

Maximum Likelihood Estimation for Semiparametric Regression Models With Panel Count Data

Panel count data, in which the observation for each study subject consists of the number of recurrent events between successive examinations, are commonly encountered in industrial reliability testing, medical research, and various other scientific investigations. We formulate the effects of potentially time-dependent covariates on one or more types of recurrent events through non-homogeneous Poisson processes with random effects. We adopt nonparametric maximum likelihood estimation under arbitrary examination schemes and develop a simple and stable EM algorithm. We show that the resulting estimators of the regression parameters are consistent and asymptotically normal, with a covariance matrix that achieves the semiparametric efficiency bound and can be estimated through profile likelihood. We evaluate the performance of the proposed methods through extensive simulation studies and present a skin cancer clinical trial.

EFFICIENT ESTIMATION OF INTEGRATED VOLATILITY FUNCTIONALS UNDER GENERAL VOLATILITY DYNAMICS

We provide an asymptotic theory for the estimation of a general class of smooth nonlinear integrated volatility functionals. Such functionals are broadly useful for measuring financial risk and estimating economic models using high-frequency transaction data. The theory is valid under general volatility dynamics, which accommodates both Itô semimartingales (e.g., jump-diffusions) and long-memory processes (e.g., fractional Brownian motions). We establish the semiparametric efficiency bound under a nonstandard nonergodic setting with infill asymptotics, and show that the proposed estimator attains this efficiency bound. These results on efficient estimation are further extended to a setting with irregularly sampled data.

Ensemble estimation and variable selection with semiparametric regression models

Summary 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.

SEMIPARAMETRIC EFFICIENCY FOR CENSORED LINEAR REGRESSION MODELS WITH HETEROSKEDASTIC ERRORS

Using a simplified approach developed by Severini and Tripathi (2001), we calculate the semiparametric efficiency bound for the finite-dimensional parameters of censored linear regression models with heteroskedastic errors. Under an additional identification at infinity type assumption, we propose an efficient estimator based on a novel result from Lewbel and Linton (2002). An extension to censored partially linear single-index models is also presented.

ASYMPTOTICALLY EFFICIENT ESTIMATION OF WEIGHTED AVERAGE DERIVATIVES WITH AN INTERVAL CENSORED VARIABLE

This paper studies the identification and estimation of weighted average derivatives of conditional location functionals including conditional mean and conditional quantiles in settings where either the outcome variable or a regressor is interval-valued. Building on Manski and Tamer (2002, Econometrica 70(2), 519–546) who study nonparametric bounds for mean regression with interval data, we characterize the identified set of weighted average derivatives of regression functions. Since the weighted average derivatives do not rely on parametric specifications for the regression functions, the identified set is well-defined without any functional-form assumptions. Under general conditions, the identified set is compact and convex and hence admits characterization by its support function. Using this characterization, we derive the semiparametric efficiency bound of the support function when the outcome variable is interval-valued. Using mean regression as an example, we further demonstrate that the support function can be estimated in a regular manner by a computationally simple estimator and that the efficiency bound can be achieved.

ON THE ASYMPTOTIC EFFICIENCY OF GMM

The efficiency of the generalized method of moment (GMM) estimator is addressed by using a characterization of its variance as an inner product in a reproducing kernel Hilbert space. We show that the GMM estimator is asymptotically as efficient as the maximum likelihood estimator if and only if the true score belongs to the closure of the linear space spanned by the moment conditions. This result generalizes former ones to autocorrelated moments and possibly infinite number of moment restrictions. Second, we derive the semiparametric efficiency bound when the observations are known to be Markov and satisfy a conditional moment restriction. We show that it coincides with the asymptotic variance of the optimal GMM estimator, thus extending results by Chamberlain (1987,Journal of Econometrics34, 305–33) to a dynamic setting. Moreover, this bound is attainable using a continuum of moment conditions.