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Multiple hypothesis testing is a fundamental problem in high-dimensional inference, with wide applications in many scientific fields. In genome-wide association studies, tens of thousands of tests are performed simultaneously to find if any single-nucleotide polymorphisms (SNPs) are associated with some traits and those tests are correlated. When test statistics are correlated, false discovery control becomes very challenging under arbitrary dependence. In this article, we propose a novel method—based on principal factor approximation—that successfully subtracts the common dependence and weakens significantly the correlation structure, to deal with an arbitrary dependence structure.We derive an approximate expression for false discovery proportion (FDP) in large-scale multiple testing when a common threshold is used and provide a consistent estimate of realized FDP. This result has important applications in controlling false discovery rate and FDP. Our estimate of realized FDP compares favorably with Efron’s approach, as demonstrated in the simulated examples. Our approach is further illustrated by some real data applications. We also propose a dependence-adjusted procedure that is more powerful than the fixed-threshold procedure. Supplementary material for this article is available online.

Estimation of longitudinal data covariance structure poses significant challenges because the data usually are collected at irregular time points. A viable semiparametric model for covariance matrixes has been proposed that allows one to estimate the variance function nonparametrically and to estimate the correlation function parametrically by aggregating information from irregular and sparse data points within each subject. But the asymptotic properties of the quasi-maximum likelihood estimator (QMLE) of parameters in the covariance model are largely unknown. We address this problem in the context of more general models for the conditional mean function, including parametric, nonparametric, or semiparametric. We also consider the possibility of rough mean regression function and introduce the difference-based method to reduce biases in the context of varying-coefficient partially linear mean regression

Motivated by recent work on studying massive imaging data in various neuroimaging studies, we propose a novel spatially varying coefficient model (SVCM) to capture the varying association between imaging measures in a three-dimensional volume (or two-dimensional surface) with a set of covariates. Two stylized features of neuorimaging data are the presence of multiple piecewise smooth regions with unknown edges and jumps and substantial spatial correlations. To specifically account for these two features, SVCM includes a measurement model with multiple varying coefficient functions, a jumping surface model for each varying coefficient function, and a functional principal component model. We develop a three-stage estimation procedure to simultaneously estimate the varying coefficient functions and the spatial correlations. The estimation procedure includes a fast multiscale adaptive estimation and

This article deals with statistical inferences based on the varying-coefficient models proposed by Hastie and Tibshirani. Local polynomial regression techniques are used to estimate coefficient functions, and the asymptotic normality of the resulting estimators is established. The standard error formulas for estimated coefficients are derived and are empirically tested. A goodness-of-fit test technique, based on a nonparametric maximum likelihood ratio type of test, is also proposed to detect whether certain coefficient functions in a varying-coefficient model are constant or whether any covariates are statistically significant in the model. The null distribution of the test is estimated by a conditional bootstrap method. Our estimation techniques involve solving hundreds of local likelihood equations. To reduce the computational burden, a one-step Newton-Raphson estimator is proposed and implemented. The resulting one