biostudies-literatureStella CMinistry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)Ministry of Economy and Competitiveness | Instituto de Salud Carlos III91https://www.ebi.ac.uk/biostudies/studies/S-EPMC12923818biostudies-literatureUnknown16(1)Previous studies have evaluated the role of the microRNA-137 (miRNA137) regulatory pathway in schizophrenia by using in silico or in vitro predicted target genes. These approaches do not capture the dynamic spatiotemporal nature of the miRNA137 regulatory pathway or tend to overestimate direct miRNA binding sites. To provide a more accurate representation of the miRNA137 pathway during human brain development, we evaluated the biological functionality of direct ex vivo miRNA137 targets previously documented in the early prenatal and adult brain. We studied the role of differential expression and genetic predisposing variation to schizophrenia and related disorders within these miRNA137 targets by gene set enrichment analyses (GSEA) and gene-set based polygenic score predictions in an indepTranslational psychiatryBiological underpinnings and genetic predisposition to schizophrenia within microrna-137 regulatory pathways across brain development.PMC12923818CD20/00118Moreno CCIBERSAM consortiumAndreu-Bernabeu AFananas LArrojo MParellada MVilella EDiaz-Caneja CMStella CVazquez-Bourgon JGurriaran XGonzalez-Pinto AEscarti MJCostas JCrespo-Facorro BMuntane GMolto MDRivero OSanchez-Gistau VMora AMartorell LGonzalez Pinto ADe Hoyos Lde la Cruz ARGonzalez-Penas JBobes JDavid-Lluesma JArango CArias BfalseBiological underpinnings and genetic predisposition to schizophrenia within microrna-137 regulatory pathways across brain development.Previous studies have evaluated the role of the microRNA-137 (miRNA137) regulatory pathway in schizophrenia by using in silico or in vitro predicted target genes. These approaches do not capture the dynamic spatiotemporal nature of the miRNA137 regulatory pathway or tend to overestimate direct miRNA binding sites. To provide a more accurate representation of the miRNA137 pathway during human brain development, we evaluated the biological functionality of direct ex vivo miRNA137 targets previously documented in the early prenatal and adult brain. We studied the role of differential expression and genetic predisposing variation to schizophrenia and related disorders within these miRNA137 targets by gene set enrichment analyses (GSEA) and gene-set based polygenic score predictions in an indep2026-01-01T00:00:00Z2026 Feb2026-07-16T14:43:42.934Z2026-07-09T11:00:22.445ZS-EPMC129238184167340010.1038/s41398-026-03859-0