Plasticizer-linked placental genes AKT1, CLEC7A, CTSS prioritized in gestational diabetes multi-omics study

Integrating Mendelian randomization and placental single-cell data, researchers identified AKT1, CLEC7A, and CTSS as plasticizer-responsive genes associated with gestational diabetes. DEHP exposure altered CLEC7A in trophoblast cells, supporting a toxicogenomic hypothesis. Causa…

• Multi-method study combined target annotation, placental bulk transcriptomics, cis-eQTL MR, Bayesian colocalization, machine learning, pathway analysis, and single-cell data; no total sample size reported in abstract.
• Among 15 genes with nominal MR associations, LASSO and random forest converged on AKT1, CLEC7A, and CTSS; AKT1 and CTSS showed concordant expression-MR direction.
• Key limitation: MR based on summary statistics from FinnGen, trophoblast validation limited to HTR-8/SVneo cell line, and two-dose DEHP design did not support concentration-response conclusion — causality not demonstrated.

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