DNA methylation signatures associated with early-onset schizophrenia in Chinese patients

Schizophrenia is a heterogeneous psychiatric disorder with diverse clinical manifestations and complex biological mechanisms, in which age-at-onset (AAO) critically influences disease trajectory. Patients with early-onset schizophrenia (EOS; AAO -5), we identified 49 differentially methylated positions (DMPs) for EOS-AOS and 126 DMPs for AAO. Genes annotated to the identified DMPs included known schizophrenia and EOS-associated loci (such as ORMDL1, ANXA4, and TRRAP), as well as novel regions linked to cognitive function and neurodevelopment (such as AKAP8L, GPRC5C, and C4orf45). Enrichment analysis implicated key biological processes, including kinase signaling, cell cycle regulation, and microRNA pathways involved in apoptosis and oncogenesis. This study reveals novel differential DNA methylation patterns associated with EOS in the Chinese population and identifies key biological pathways potentially underlying its pathogenesis.