arXiv subjects

Samuel Anyaso-Samuel

Publications and source records attributed to Samuel Anyaso-Samuel.

4 recordsLinked to original sources

arXiv2026

Using Importance Sampling to Estimate $p$-values in All-Subset Meta-Analysis, with Applications to Single-Cell eQTL Mapping

Pooling genome-wide association studies of multiple related traits can substantially increase power for detecting genetic variants with pleiotropic effects. ASSET, which exhaustively searches all subsets of studies for association signals, has been widely used to detect modest effects and improve interpretability. Under a normality assumption, ASSET computes p-values via an analytic approximation that accounts for multiple testing. However, this approximation has been evaluated only in limited scenarios and for p-values no smaller than $10^{-3}$. A systematic assessment in the extreme tail is therefore needed, yet na\"ive Monte Carlo methods would require prohibitively many simulations. We develop a computationally efficient importance-sampling (IS) algorithm that provides accurate ASSET p-value estimates for both independent and overlapping studies, achieving substantial efficiency gains over na\"ive Monte Carlo, particularly for very small p-values. Using IS, we show that ASSET's analytic approximation is highly accurate across nearly the entire p-value range when normality holds. In contrast, when normality is violated (due to small sample sizes, low-frequency variants, or non-normal traits), ASSET p-values can be inflated or deflated by orders of magnitude, whereas our IS approach remains accurate. We illustrate the method through applications to single-cell eQTL mapping using peripheral blood mononuclear cells from the OneK1K cohort and lung cells from a Korean population.

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arXiv2024

Nonparametric estimation of a state entry time distribution conditional on a "past" state occupation in a progressive multistate model with current status data

Case-I interval-censored (current status) data from multistate systems are often encountered in biomedical and epidemiological studies. In this article, we focus on the problem of estimating state entry distribution and occupation probabilities, contingent on a preceding state occupation. This endeavor is particularly complex owing to the inherent challenge of the unavailability of directly observed counts of individuals at risk of transitioning from a state, due to severe interval censoring. We propose two nonparametric approaches, one using the fractional at-risk set approach recently adopted in the right-censoring framework and the other a new estimator based on the ratio of marginal state occupation probabilities. Both estimation approaches utilize innovative applications of concepts from the competing risks paradigm. The finite-sample behavior of the proposed estimators is studied via extensive simulation studies where we show that the estimators based on severely censored current status data have good performance when compared with those based on complete data. We demonstrate the application of the two methods to analyze data from patients diagnosed with breast cancer.

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arXiv2023

Pseudo-value regression of clustered multistate current status data with informative cluster sizes

Multistate current status (CS) data presents a more severe form of censoring due to the single observation of study participants transitioning through a sequence of well-defined disease states at random inspection times. Moreover, these data may be clustered within specified groups, and informativeness of the cluster sizes may arise due to the existing latent relationship between the transition outcomes and the cluster sizes. Failure to adjust for this informativeness may lead to a biased inference. Motivated by a clinical study of periodontal disease (PD), we propose an extension of the pseudo-value approach to estimate covariate effects on the state occupation probabilities (SOP) for these clustered multistate CS data with informative cluster or intra-cluster group sizes. In our approach, the proposed pseudo-value technique initially computes marginal estimators of the SOP utilizing nonparametric regression. Next, the estimating equations based on the corresponding pseudo-values are reweighted by functions of the cluster sizes to adjust for informativeness. We perform a variety of simulation studies to study the properties of our pseudo-value regression based on the nonparametric marginal estimators under different scenarios of informativeness. For illustration, the method is applied to the motivating PD dataset, which encapsulates the complex data-generation mechanism.

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arXiv2023

Adjusting for informative cluster size in pseudo-value based regression approaches with clustered time to event data

Informative cluster size (ICS) arises in situations with clustered data where a latent relationship exists between the number of participants in a cluster and the outcome measures. Although this phenomenon has been sporadically reported in statistical literature for nearly two decades now, further exploration is needed in certain statistical methodologies to avoid potentially misleading inferences. For inference about population quantities without covariates, inverse cluster size reweightings are often employed to adjust for ICS. Further, to study the effect of covariates on disease progression described by a multistate model, the pseudo-value regression technique has gained popularity in time-to-event data analysis. We seek to answer the question: "How to apply pseudo-value regression to clustered time-to-event data when cluster size is informative?" ICS adjustment by the reweighting method can be performed in two steps; estimation of marginal functions of the multistate model and fitting the estimating equations based on pseudo-value responses, leading to four possible strategies. We present theoretical arguments and thorough simulation experiments to ascertain the correct strategy for adjusting for ICS. A further extension of our methodology is implemented to include informativeness induced by the intra-cluster group size. We demonstrate the methods in two real-world applications: (i) to determine predictors of tooth survival in a periodontal study, and (ii) to identify indicators of ambulatory recovery in spinal cord injury patients who participated in locomotor-training rehabilitation.

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