Haochen Lei | Searcharxiv

arXiv2026

Heritability: A Counterfactual Perspective

Heritability is a central concept in the long-standing debate about nature versus nurture in biological and social sciences. However, existing notions of heritability are based on strong assumptions and do not use explicit causal models. We propose a new, counterfactual definition of heritability by adopting the potential outcomes model in causal inference. Our counterfactual heritability measures the importance of genetic inheritance by the average magnitude of difference between an individual with their hypothetical ``non-identical twin'' that is exposed to the exact same environment. We provide bounds on the counterfactual heritability that can, in principle, be computed from observational data. We then compare counterfactual heritability and its associated bounds with common notions of heritability in population-based studies, twin and sibling studies, and plant breeding experiments. Our results and comparisons highlight the importance of clarifying the causal structural assumptions and counterfactual comparisons in reasoning about heritability.

stat.AP↗

arXiv2023

A robust and powerful method for assessing replicability of high dimensional data

Identifying signals that replicate across multiple studies is essential for establishing robust scientific evidence, yet existing methods for high-dimensional replicability analysis either rely on restrictive modeling assumptions, are limited to two-study settings, or lack statistical power. We propose a general empirical Bayes framework for multi-study replicability analysis that jointly models summary-level $p$-values while explicitly accounting for between-study heterogeneity. Within each study, non-null $p$-value densities are estimated nonparametrically under monotonicity constraints, enabling flexible and tuning-free inference. For two studies, we develop a local false discovery rate (Lfdr) statistic for the composite null of non-replicability and establish identifiability, consistency, and a cubic-rate convergence of the nonparametric MLE, along with minimax optimality. Extending replicability analysis to $n$ studies typically requires estimating $2^n$ latent configurations, which is computationally infeasible. To address this challenge, we introduce a scalable pairwise rejection strategy that decomposes the exponentially large composite null into disjoint components, yielding linear complexity in the number of studies. We prove asymptotic FDR control under mild regularity conditions and show that Lfdr-based thresholding is power-optimal. Extensive simulations demonstrate that our method provides substantial power gains while maintaining valid FDR control, outperforming state-of-the-art alternatives across a wide range of scenarios. Applying our framework to East Asian- and European-ancestry genome-wide association studies of type 2 diabetes reveals replicable genetic associations that competing approaches fail to detect, illustrating the method's practical utility in large-scale biomedical research.

stat.ME↗