rs3755557

This candidate gene association study examined 18 SNPs in tau phosphorylation pathway genes (kinases and phosphatases) in relation to cerebrospinal fluid (CSF) tau levels in 101 Alzheimer's disease (AD) patients and 169 cognitively normal controls. Two SNPs significantly correlated with CSF tau levels after multiple comparison correction: rs7768046 in the FYN kinase gene (associated with increased CSF t-tau in AD, P=0.0007 Holm-corrected) and rs913275 in the PPP2R4 phosphatase gene (associated with increased CSF p-tau and t-tau in AD, P=0.0024 Holm-corrected). These findings suggest that genetic variation in genes regulating tau phosphorylation influences CSF tau levels in an AD-associated manner.

This systematic review of 98 studies examined biological predictors of clozapine response in treatment-resistant schizophrenia patients. Of 379 different gene variants investigated across 70 genetic studies, only three variants (DRD3 Ser9Gly rs6280, HTR2A His452Tyr, and GNB3 C825T) achieved independent replication. Non-genetic predictors included higher prefrontal cortical volumes and lower HVA:5-HIAA ratio in cerebrospinal fluid.

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).

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.

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).

A population-based case-control study of 832 bladder cancer cases and 1,191 controls examining SNPs in cancer-regulatory pathways identified increased risk associated with MTHFD2 (OR 1.7, 95% CI 1.3-2.3), TEP1 (OR 1.8, 95% CI 1.2-2.6), and decreased risk with IL8RB (OR 0.6, 95% CI 0.5-0.9). Survival analysis found shorter survival with CASP9 variants (HR 1.8, 95% CI 1.1-3.0) and longer survival with EPHX1 variants (HR 0.4, 95% CI 0.2-0.8). Multi-SNP combinations in metabolism, DNA repair, telomerase, and apoptosis pathways were also predictive of bladder cancer risk and prognosis.

A case-control and family-based association study examining 12 genetic markers across the GSK3β gene for association with schizophrenia and clozapine response. Three markers showed significant genotypic association with schizophrenia in the case-control sample: rs7624540 (χ² = 8.28, p = 0.016), rs4072520 (χ² = 9.94, p = 0.007), and rs6779828 (χ² = 6.83, p = 0.033). No associations were found in family-based analysis or with clozapine treatment response.