Immune cell-based transcriptomic Mendelian randomization and colocalization study on type 1 diabetes.

ABSTRACT:

Background

Interventions to prevent type 1 diabetes (T1D), an immune-mediated disease requiring lifelong treatment, remain limited. We sought to identify novel therapeutic targets for T1D through Mendelian randomization and colocalization using immune cell-derived instruments.

Methods

We selected locally acting genetic variants from 14 transcriptomic studies to instrument expression of 8998 genes measured in immune cell types. Outcome associations were obtained from a T1D genome-wide association study that included 18,942 cases and 501,638 controls. Follow-up analyses included assessments of horizontal pleiotropy and novelty, as well as phenome-wide scans with colocalization (PheWAS-coloc) of instrumental variants.

Results

We prioritized 21 genes (CLNK, EED, LZTFL1, M

SUBMITTER: Sklar J 

PROVIDER: S-EPMC12751804 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature