Donor-associated variation outweighs PMOS status in patient-derived iPSC transcriptomes: a genotyped, BMI-adjusted study of 14 lines

In 14 BMI-matched, genotyped patient-derived iPSC lines from women with PMOS, no gene showed differential expression versus controls (FDR < 0.1).

• Why it matters: Prior small donor comparisons reported many expression differences, but inter-donor variation could masquerade as a PMOS signal; this study tests detectability in a larger, balanced panel.
• What they did: Bulk RNA-seq of 16,489 expressed genes from CRISPR-activation, transgene-free iPSC lines (7 PMOS, 7 controls) was modeled against diagnosis, hormones, metabolic traits, age, and XIST status, with permutation-calibrated gene-set tests and exact 3,432 group splits.
• The result: PMOS-associated genes and Hallmark pathways were not enriched, diagnosis and traits explained no more variance than chance, and PRS showed only partial separation (OR 1.81 per SD; AUC 0.65) despite full overlap in iPSC donors.

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