biostudies-literatureUnknown229(5)Almodovar-Paya CUniversitat de BarcelonaThe expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1's activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ) risk, symptomatology, and brain differences. However, research on how they synergistically modulate these phenotypes is scarce. We aimed to study whether the genetic epistasis between these genes affects the risk and clinical presentation of the disorder via its effect on brain structure. First, we tested the epistatic effect of NRNBrain structure & function1299-1315https://www.ebi.ac.uk/biostudies/studies/S-EPMC11147852biostudies-literatureNRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia.PMC11147852Canales-Rodriguez EJMadre MRamiro NCallado LFSoler-Vidal JGallego CGiralt-Lopez MPomarol-Clotet EOscoz-Irurozqui MAlmodovar-Paya CFatjo-Vilas MGuardiola-Ripoll MArias BfalseNRN1 epistasis with BDNF and CACNA1C: mediation effects on symptom severity through neuroanatomical changes in schizophrenia.The expression of Neuritin-1 (NRN1), a neurotrophic factor crucial for neurodevelopment and synaptic plasticity, is enhanced by the Brain Derived Neurotrophic Factor (BDNF). Although the receptor of NRN1 remains unclear, it is suggested that NRN1's activation of the insulin receptor (IR) pathway promotes the transcription of the calcium voltage-gated channel subunit alpha1 C (CACNA1C). These three genes have been independently associated with schizophrenia (SZ) risk, symptomatology, and brain differences. However, research on how they synergistically modulate these phenotypes is scarce. We aimed to study whether the genetic epistasis between these genes affects the risk and clinical presentation of the disorder via its effect on brain structure. First, we tested the epistatic effect of NRN2024-01-01T00:00:00Z2024 Jun2026-06-01T18:51:00.392Z2026-05-19T03:07:10.972ZS-EPMC111478523872000410.1007/s00429-024-02793-5