rs3924999

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

A targeted sequencing study of 115 patients with bipolar disorder and depression identified genetic variants in NRG1, PIP4K2A, and HTR2C associated with treatment response and disease severity. The allele C of rs35641374 (NRG1) was associated with longer intervals between depressive episodes (p=4.37e-07), while the allele C of rs10508649 (PIP4K2A) was associated with longer intervals between manic/mixed episodes (p=0.000309) and treatment resistance assessed by CGI-I scale (p=0.000943). The allele A of rs2248440 (HTR2C) was associated with higher depression severity (p=0.003).

This targeted sequencing association study of 115 psychiatric patients and 34 controls identifies NRG1, PIP4K2A, and HTR2C as candidate biomarker genes for antidepressant treatment response and mood disorder recurrence. Key findings include rs35641374 (NRG1) associated with longer time to depressive recurrence in bipolar disorder (p=4.37e-07), rs61731109 and rs10508649 (PIP4K2A) associated with antidepressant non-response (p=0.00111 and p=0.000943), and rs2248440 (HTR2C) associated with higher depression severity (p=0.003).

This study examined NRG1, DAOA, and DISC1 gene polymorphisms and expression in 195 Chinese Han individuals (18 ultra-high risk for psychosis, 61 first-degree relatives, 55 first-episode psychosis, 61 healthy controls). Rs3918341 in DAOA was associated with UHR susceptibility (OR=3.68, p<0.001). Epistatic analysis showed interactions between NRG1 and DAOA, and NRG1 and DISC1 genes in UHR risk. NRG1 mRNA was significantly downregulated in the UHR group compared to healthy controls and first-episode psychosis patients.