A cross-tissue transcriptome-wide association study identifies novel candidate genes associated with brain glymphatic system function.

ABSTRACT: The glymphatic system plays a key role in brain waste clearance, but its genetic regulation remains poorly understood. Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index is a non-invasive imaging biomarker to asses glymphatic system activity. We integrated mean DTI-ALPS genome-wide association study (GWAS) data from 31,021 individuals of European ancestry with GTEx v8 multi-tissue eQTL data to perform transcriptome-wide association studies (TWAS) using Unified Test for Molecular Signature (UTMOST) and Functional Summary-based Imputation (FUSION). Gene-level associations were further validated by Multi-marker Analysis of Genomic Annotation (MAGMA). Causal inference was conducted using cis-Mendelian randomization (cis-MR) and summary-data-based Mendelian randomizat

SUBMITTER: Zhu X 

PROVIDER: S-EPMC12681178 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature