Univariate-Guided Sparse Regression for Biobank-Scale High-Dimensional Omics Data
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| Main Authors: | , , , , , , , |
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| Format: | Preprint |
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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 |
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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 |