| Title: | The Effect of Alcohol Intake on Brain White Matter Microstructural Integrity: A New Causal Inference Framework for Incomplete Phenomic Data |
| Journal: | Journal of the American Statistical Association |
| Published: | 20 Oct 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41122496/ |
| DOI: | https://doi.org/10.1080/01621459.2025.2542553 |
Publication 17775
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Although substance use, such as alcohol intake, is known to be associated with cognitive decline during aging, its direct influence on the central nervous system remains incompletely understood. In this study, we investigate the influence of alcohol intake frequency on reduction of brain white matter microstructural integrity in the fornix, a brain region considered a promising marker of age-related microstructural degeneration, using a large UK Biobank (UKB) cohort with extensive phenomic data reflecting a comprehensive lifestyle profile. Two major challenges arise: (a) potentially nonlinear confounding effects from phenomic variables and (b) a limited proportion of participants with complete phenomic data. To address these challenges, we develop a novel ensemble learning framework tailored for robust causal inference and introduce a data integration step to incorporate information from UKB participants with incomplete phenomic data, improving estimation efficiency. Our analysis reveals that daily alcohol intake may significantly reduce fractional anisotropy, a neuroimaging-derived measure of white matter structural integrity, in the fornix and increase systolic and diastolic blood pressure levels. Moreover, extensive numerical studies demonstrate the superiority of our method over competing approaches in terms of estimation bias, while outcome regression-based estimators may be preferred when minimizing mean squared error is prioritized. Supplementary materials for this article are available online, including a standardized description of the materials available for reproducing the work.</p>
6 Authors
- Chixiang Chen
- Shuo Chen
- Zhenyao Ye
- Xu Shi
- Tianzhou Ma
- Michelle Shardell
Enabling scientific discoveries that improve human health