Methylome-wide and meQTL analysis helps to distinguish treatment response from non-response and pathogenesis markers in schizophrenia

• DOI: 10.3389/fpsyt.2024.1297760
• Publication Date: 2024-03-07T04:28:11Z
• Authors: Binithamol K. Pol...; Neetha N. Vellich...; Indu V. Nair; Chandrasekharan M...; Moinak Banerjee
• Keywords: Pathogenesis; Drug response

Schizophrenia is a complex condition with entwined genetic and epigenetic risk factors, posing challenge to disentangle the intermixed pathological therapeutic signatures. To resolve this, we performed 850K methylome-wide 700K genome-wide studies on same set of schizophrenia patients by stratifying them into responders, non-responders, drug-naïve patients. The key genes that signified response were followed up using real-time gene expression understand effect antipsychotics at transcription level. study primarily implicates hypermethylation in hypomethylation drug-non-responsive state. Several differentially methylated sites regions colocalized association (GWAS) variants, supporting convoluted gene-environment association. Gene ontology protein-protein interaction (PPI) network analyses revealed distinct patterns differentiated treatment from drug resistance. highlights strong involvement several processes related nervous system development, cell adhesion, signaling antipsychotic response. ability medications alter pathology modulating or methylation evident general increase markers histone modifiers decrease class II human leukocyte antigen (HLA) following varying concentrations like clozapine, olanzapine, risperidone, haloperidol. indicates directional overlap between pathogenesis response, thereby suggesting careful distinction In addition, there need trade-off observations. It suggested methylomic changes brought about drugs evaluation for their positive effects pathogenesis, course disease progression, symptom severity, side effects, refractoriness.