PRISM-xQTL: Pleiotropic Relationships Integrated with System-level Multiomic QTL analysis for causal genes and molecular mediators in Alzheimer's disease.

ABSTRACT:

Introduction

Most Alzheimer's disease (AD) risk variants identified by genome-wide association studies (GWAS) reside in noncoding regions, complicating causal interpretation.

Methods

We developed PRISM-xQTL (Pleiotropic Relationships Integrated with System-level Multiomic QTL), integrating pleiotropy, co-localization, Mendelian randomization, and mediation analyses across multiomic quantitative trait loci (QTLs; expression QTL [eQTL], methylation QTL [meQTL], splicing QTL [sQTL], proteomic [pQTL], single-cell [sc-eQTL]). Seventy pleiotropic single-nucleotide polymorphisms (SNPs) shared between AD and 11 immune disorders were analyzed. AlphaGenome assessed functional regulation, and The Alzheimer's Cell Atlas (TACA) database was used for drug-target relevance of FCER1G.

Re

SUBMITTER: Enduru N 

PROVIDER: S-EPMC12854938 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature