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Improving estimation efficiencies for family-based GWAS by integrating large external data

Family-based genome-wide association studies (GWAS) can separate direct from indirect genetic effects such as genetic nurture, population stratification, and assortative mating, yet these designs often suffer from limited statistical power because …

Effects of Distance Metrics and Scaling on the Perturbation Discrimination Score

The Perturbation Discrimination Score (PDS) is increasingly used to evaluate whether predicted perturbation effects remain distinguishable, including in Systema and the Virtual Cell Challenge. However, its behavior in high-dimensional gene-expression …

Validity and Power of Heavy-Tailed Combination Tests under Asymptotic Dependence

Heavy-tailed combination tests, such as the Cauchy combination test and harmonic mean p-value method, are widely used for testing global null hypotheses by aggregating dependent p-values. However, their theoretical guarantees under general dependence …

Sensitivity Analysis for the Test-Negative Design

The test-negative design has become popular for evaluating the effectiveness of post-licensure vaccines using observational data. In addition to its logistical convenience on data collection, the design is also believed to control for the …

Validity and Interpretation of Two-Sample Mendelian Randomization with Binary Traits

Two-sample Mendelian randomization (MR) is widely applied to binary exposures and outcomes. Yet standard MR models rely on linear effect assumptions that are difficult to interpret for binary traits. Although liability-based interpretations have been …