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What is Learnable in Valiant's Theory of the Learnable? Learning Perturbations to Extrapolate Your LLM Byzantine-Robust Distributed Sparse Learning Revisited The Sample Complexity of Multiple Change Point Identification under Bandit Feedback A proximal gradient algorithm for composite log-concave sampling Model-based Bootstrap of Controlled Markov Chains Approximation of Maximally Monotone Operators : A Graph Convergence Perspective Posterior Contraction Rates for Sparse Kolmogorov-Arnold Networks in Anisotropic Besov Spaces MIST: Reliable Streaming Decision Trees for Online Class-Incremental Learning via McDiarmid Bound A Spectral Framework for Closed-Form Relative Density Estimation Fast Rates for Offline Contextual Bandits with Forward-KL Regularization under Single-Policy Concentrability Higher-Order Equilibrium Tracking for EM-Compressible Online Estimation Scaling Limits of Long-Context Transformers A Note on Non-Negative $L_1$-Approximating Polynomials Susceptibilities and Patterning: A Primer on Linear Response in Bayesian Learning Linear Response Estimators for Singular Statistical Models Statistical inference with belief functions: A survey Robust stochastic first order methods in heavy-tailed noise via medoid mini-batch gradient sampling Every Feedforward Neural Network Definable in an o-Minimal Structure Has Finite Sample Complexity Adaptive auditing of AI systems with anytime-valid guarantees Locally Near Optimal Piecewise Linear Regression in High Dimensions via Difference of Max-Affine Functions Risk-Controlled Post-Processing of Decision Policies Covariate Balancing and Riesz Regression Should Be Guided by the Neyman Orthogonal Score in Debiased Machine Learning A Unified Pair-GRPO Family: From Implicit to Explicit Preference Constraints for Stable and General RL Alignment Time-Inhomogeneous Preconditioned Langevin Dynamics A Fine-Grained Understanding of Uniform Convergence for Halfspaces CITE: Anytime-Valid Statistical Inference in LLM Self-Consistency Ratio-based Loss Functions Optimal Confidence Band for Kernel Gradient Flow Estimator A renormalization-group inspired lattice-based framework for piecewise generalized linear models
A statistical framework for GWAS of high dimensional phen...
Weiqiong Huang, Emily C. Hector, Joshua Cape, Chris McKennan · 2023-03-18 · via math.ST updates on arXiv.org

The recent explosion of genetic and high dimensional biobank and 'omic' data has provided researchers with the opportunity to investigate the shared genetic origin (pleiotropy) of hundreds to thousands of related phenotypes. However, existing methods for multi-phenotype genome-wide association studies (GWAS) do not model pleiotropy, are only applicable to a small number of phenotypes, or provide no way to perform inference. To add further complication, raw genetic and phenotype data are rarely observed, meaning analyses must be performed on GWAS summary statistics whose statistical properties in high dimensions are poorly understood. We therefore developed a novel model, theoretical framework, and set of methods to perform Bayesian inference in GWAS of high dimensional phenotypes using summary statistics that explicitly model pleiotropy, beget fast computation, and facilitate the use of biologically informed priors. We demonstrate the utility of our procedure by applying it to metabolite GWAS, where we develop new nonparametric priors for genetic effects on metabolite levels that use known metabolic pathway information and foster interpretable inference at the pathway level.