International journal of general medicine
Multi-Omics Prioritization and Clinical Evaluation of CYP4V2 as a Candidate Biomarker in Venous Thromboembolism
Por Zhang C, Xu J, Zhang M y 7 más.
Contenido en inglés
Resumen
Background
Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, has a substantial genetic component, but the effector genes and clinically relevant biomarkers remain incompletely defined.
Methods
We analyzed FinnGen R12 genome-wide association study (GWAS) summary statistics for VTE and its subphenotypes. The Mixture model for estimating polygenicity and discoverability (MiXeR) was used to characterize the shared genetic architecture between deep vein thrombosis and pulmonary embolism. Cross-tissue Unified Test for Molecular SignaTures (UTMOST) and single-tissue Functional Summary-based Imputation (FUSION) transcriptome-wide association analyses were integrated with Multi-marker Analysis of GenoMic Annotation (MAGMA) gene and pathway analyses to prioritize candidate genes. FUSION conditional and joint analysis was applied to evaluate locus-level independence. Single-variant cis-expression quantitative trait locus (cis-eQTL)-based Mendelian randomization (MR) with Steiger directionality testing was performed for CYP4V2. External validation included GSE48000 whole-blood expression analysis, Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) immune deconvolution, and serum CYP4V2 measurement by enzyme-linked immunosorbent assay (ELISA) in an independent clinical cohort.