ABSTRACT
Genome-wide association study (GWAS) has seen great strides in revealing initial insights into the genetic architecture of Parkinson's disease (PD). Since GWAS signals often reside in non-coding regions, relatively few of the associations have implicated specific biological mechanisms. Here, we aimed to integrate the GWAS results with large-scale expression quantitative trait loci (eQTL) in 13 brain tissues to identify candidate causal genes for PD. We conducted a transcriptome-wide association study (TWAS) for PD using the summary statistics of over 480,000 individuals from the most recent PD GWAS. We identified 18 genes significantly associated with PD after Bonferroni corrections. The most significant gene, LRRC37A2, was associated with PD in all 13 brain tissues, such as in the hypothalamus (P = 6.12 × 10-22) and nucleus accumbens basal ganglia (P = 5.62 × 10-21). We also identified eight conditionally independent genes, including four new genes at known PD loci: CD38, LRRC37A2, RNF40, and ZSWIM7. Through conditional analyses, we demonstrated that several of the GWAS significant signals on PD could be driven by genetically regulated gene expression. The most significant TWAS gene LRRC37A2 accounts for 0.855 of the GWAS signal at its loci, and ZSWIM7 accounts for all the GWAS signals at its loci. We further identified several phenotypes previously associated with PD by querying the single nucleotide polymorphisms (SNPs) in the final model of the identified genes in phenome databases. In conclusion, we prioritized genes that are likely to affect PD by using a TWAS approach and identified phenotypes associated with PD.
ABSTRACT
A number of patients with meningiomas and psychiatric disorders will suffer psychiatric symptom recurrence following tumorectomies. The present study reported a retrospective analysis regarding 42 cases of patients with meningiomas using complete clinical follow-up data from June 2005 to June 2013. The patients were divided into the systemic antipsychotic (SP) group (n=20) following 6months of postoperative SP therapy and the none-SP (NSP) group (n=22), who did not receive postoperative antipsychotic treatment. Patients were assessed using the Positive and Negative Syndrome Scale (PANSS) and Brief Psychiatric Rating Scale (BPRS) at the time points of prior to surgery, immediately following surgery, and 6 months, 12 months and 3 years following surgery. The effective rate, recurrence rate, rehospitalization rate and survival analysis were calculated. The BPRS score and PANSS scores (including PANSS positive, PANSS negative, PANSS general psychopathology and PANSS overall) in the SP group at 6 months, 12 months and 3 years following surgery were significantly decreased compared with the NSP group (P<0.05). The effective rate was 95, 90 and 90% at 6 months, 12 months and 3 years, respectively, in the SP group, whilst it was 68.2, 63.6 and 59%, respectively, in the NSP group, which was statistically significant (χ2=4.89, χ2=4.01 and χ2=5.12; P<0.05). The recurrence rate of the SP group was 0, 5 and 10% at 6 months, 12 months and 3 years, respectively, whilst in the NSP group it was 22.7, 31.8 and 54.5%, respectively, which was statistically significant (χ2=5.16, χ2=4.89 and χ2=9.34; P<0.05). The rehospitalization rate of the SP group was 0, 0 and 5% at 6 months, 12 months and 3 years, respectively, whilst in the NSP group it was 13.6, 22.7 and 36.4%, respectively, and the data at 12 months and 3 years was statistically significant (χ2=5.16 and χ2=6.12; P<0.05). Kaplan-Meier survival analysis indicated that the accumulative survival rates of recurrence and rehospitalization in the SP group were improved compared with the NSP group. The log-rank of recurrence was χ2=9.369 (P=0.002) and the log-rank of rehospitalization was χ2=6.330 (P=0.012). In conclusion, postoperative SP therapy is of great importance to the consolidation of mental symptoms in patients with meningiomas and psychiatric symptoms, and it may significantly reduce the recurrence and rehospitalization rates.
