Univariate-Guided Sparse Regression for Biobank-Scale High-Dimensional Omics Data

Fuente: arXiv
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Main Authors: Richland, Joshua, Kiiskinen, Tuomo, Wang, William, Lu, Sophia, Narasimhan, Balasubramanian, Hastie, Trevor, Rivas, Manuel, Tibshirani, Robert
Format: Preprint
Published: 2025
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author Richland, Joshua
Kiiskinen, Tuomo
Wang, William
Lu, Sophia
Narasimhan, Balasubramanian
Hastie, Trevor
Rivas, Manuel
Tibshirani, Robert
author_facet Richland, Joshua
Kiiskinen, Tuomo
Wang, William
Lu, Sophia
Narasimhan, Balasubramanian
Hastie, Trevor
Rivas, Manuel
Tibshirani, Robert
contents We present a scalable framework for computing polygenic risk scores (PRS) in high-dimensional genomic settings using the recently introduced Univariate-Guided Sparse Regression (uniLasso). UniLasso is a two-stage penalized regression procedure that leverages univariate coefficients and magnitudes to stabilize feature selection and enhance interpretability. Building on its theoretical and empirical advantages, we adapt uniLasso for application to the UK Biobank, a population-based repository comprising over one million genetic variants measured on hundreds of thousands of individuals from the United Kingdom. We further extend the framework to incorporate external summary statistics to increase predictive accuracy. Our results demonstrate that uniLasso attains predictive performance comparable to standard Lasso while selecting substantially fewer variants, yielding sparser and more interpretable models. Moreover, it exhibits superior performance in estimating PRS relative to its competitors, such as PRS-CS. Integrating external scores further improves prediction while maintaining sparsity.
format Preprint
id arxiv_https___arxiv_org_abs_2511_22049
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle Univariate-Guided Sparse Regression for Biobank-Scale High-Dimensional Omics Data
Richland, Joshua
Kiiskinen, Tuomo
Wang, William
Lu, Sophia
Narasimhan, Balasubramanian
Hastie, Trevor
Rivas, Manuel
Tibshirani, Robert
Methodology
62
We present a scalable framework for computing polygenic risk scores (PRS) in high-dimensional genomic settings using the recently introduced Univariate-Guided Sparse Regression (uniLasso). UniLasso is a two-stage penalized regression procedure that leverages univariate coefficients and magnitudes to stabilize feature selection and enhance interpretability. Building on its theoretical and empirical advantages, we adapt uniLasso for application to the UK Biobank, a population-based repository comprising over one million genetic variants measured on hundreds of thousands of individuals from the United Kingdom. We further extend the framework to incorporate external summary statistics to increase predictive accuracy. Our results demonstrate that uniLasso attains predictive performance comparable to standard Lasso while selecting substantially fewer variants, yielding sparser and more interpretable models. Moreover, it exhibits superior performance in estimating PRS relative to its competitors, such as PRS-CS. Integrating external scores further improves prediction while maintaining sparsity.
title Univariate-Guided Sparse Regression for Biobank-Scale High-Dimensional Omics Data
topic Methodology
62
url https://arxiv.org/abs/2511.22049