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Brendon Chau

Publications and source records attributed to Brendon Chau.

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Debiased Machine Learning for Partially Linear Accelerated Failure Time Models

The Cox model remains the default for survival analysis, but the proportional hazards assumption is often violated and hazard ratios can be difficult to interpret. Accelerated failure time (AFT) models provide an intuitive time-scale alternative, yet flexible covariate adjustment while preserving valid inference on a target exposure remains challenging. For the partially linear AFT model under right censoring, a rank-based debiased machine learning (DML) framework remains undeveloped: the rank-based pairwise moment is not Neyman orthogonal and standard cross-fitting does not directly apply to U-statistics. We develop the first such framework by combining an orthogonalized rank-based U-statistic, a censoring-corrected influence function, and block-pairwise cross-fitting, yielding valid inference under flexible nuisance estimation. Simulations and an application to All of Us electronic health record data demonstrate finite-sample performance and practical utility.

stat.ME

Estimating heritability of survival traits using censored multiple variance component model

Characterizing the genetic basis of survival traits, such as age at disease onset, is critical for risk stratification, early intervention, and elucidating biological mechanisms that can inform therapeutic development. However, time-to-event outcomes in human cohorts are frequently right-censored, complicating both the estimation and partitioning of total heritability. Modern biobanks linked to electronic health records offer the unprecedented power to dissect the genetic basis of age-at-diagnosis traits at large scale. Yet, few methods exist for estimating and partitioning the total heritability of censored survival traits. Existing methods impose restrictive distributional assumptions on genetic and environmental effects and are not scalable to large biobanks with a million subjects. We introduce a censored multiple variance component model to robustly estimate the total heritability of survival traits under right-censoring. We demonstrate through extensive simulations that the method provides accurate total heritability estimates of right-censored traits at censoring rates up to 80% given sufficient sample size. The method is computationally efficient in estimating one hundred genetic variance components of a survival trait using large-scale biobank genotype data consisting of a million subjects and a million SNPs in under nine hours, including uncertainty quantification. We apply our method to estimate the total heritability of four age-at-diagnosis traits from the UK Biobank study. Our results establish a scalable and robust framework for heritability analysis of right-censored survival traits in large-scale genetic studies.

stat.ME