Here the authors analyse rare coding variants to identify schizophrenia risk genes. Associations are reported at exome-wide significance for STAG1 and ZNF136, and at a false discovery rate of 5% for SLC6A1, PCLO, ZMYND11, BSCL2, KLC1 and CGREF1.

Alzheimer’s disease (AD) remains an incurable neurodegenerative disorder with an elusive pathogenesis, where emerging evidence implicates metabolic dysregulation and ferroptosis in neuronal loss. Although the BSCL2 gene, which encodes Seipin, is crucial for lipid metabolism, its specific role in the progression of AD remains undefined. This study employed Mendelian randomization (MR) analysis, in vivo APP/PS1 mouse models, and in vitro BV2 microglial assays to elucidate the mechanistic axis linking BSCL2, metabolites, and ferroptosis in AD. MR analysis demonstrated a causal relationship between genetically predicted elevated BSCL2 expression and an increased risk of AD, partially mediated by glycine. Supporting these genetic findings, stereotactic knockdown of Seipin in the hippocampus of APP/PS1 mice significantly ameliorated cognitive deficits without inducing systemic metabolic toxicity. Mechanistically, Seipin deficiency reduced ferroptosis in both AD mouse brains and Aβ

Maintaining the metabolic homeostasis of fatty acids is crucial for human health. Excess fatty acids

Maintaining the metabolic homeostasis of fatty acids is crucial for human health. Excess fatty acids