Genetic correlation, shared loci, but no causality between bipolar disorder and inflammatory bowel disease: A genome-wide pleiotropic analysis.

BACKGROUND AND AIMS: The comorbidity between bipolar disorder (BD) and inflammatory bowel disease (IBD) has been widely reported in observational studies. However, unclear whether this comorbidity reflects a shared genetic architecture. METHODS: Leveraging large-scale genome-wide association study (GWAS) summary statistics of BD, IBD and its subtypes, ulcerative colitis (UC) and Crohn's disease (CD), we performed a genome-wide pleiotropic analysis to estimate heritability and genetic correlation, identify pleiotropy loci/genes, and explore the shared biological pathway. Mendelian randomization (MR) studies were subsequently employed to infer whether the potential causal relationship is present. RESULTS: We found a positive significant genetic correlation between BD and IBD (rg = 0.10, P = 7.00 × 10-4), UC (rg = 0.09, P = 2.90 × 10-3), CD (rg = 0.08, P = 6.10 × 10-3). In cross-trait meta-analysis, a total of 29, 24, and 23 independent SNPs passed the threshold for significant association between BD and IBD, UC, and CD, respectively. We identified five novel pleiotropy genes including ZDHHC2, SCRN1, INPP4B, C1orf123, and BRD3 in both BD and IBD, as well as in its subtypes UC and CD. Pathway enrichment analyses revealed that those pleiotropy genes were mainly enriched in several immune-related signal transduction pathways and cerebral disease-related pathways. MR analyses provided no evidence for a causal relationship between BD and IBD. CONCLUSION: Our findings corroborated that shared genetic basis and common biological pathways may explain the comorbidity of BD and IBD. These findings further our understanding of shared genetic mechanisms underlying BD and IBD, and potentially provide points of intervention that may allow the development of new therapies for these co-occurrent disorders.

[Application of imatinib plus Hyper-CVAD chemotherapy regimen in patients with Ph chromosome positive acute lymphocytic leukemia].

OBJECTIVE: To report the efficacy and safety of imatinib plus Hyper-CVAD chemotherapy regimen in the treatment of patients with ph chromosome positive acute lymphocytic leukemia (Ph(+)ALL). METHODS: A sequential 2-year and 8-cycle treatment of imatinib plus Hyper-CVAD (A/B program) was administrated in 18 Ph(+)ALL patients treated at our hospital since January 2005 to January 2010. And another 18 Ph(+)ALL patients undergoing no allogeneic hematopoietic stem cell transplantation were selected as controls. RESULTS: Among 18 patients on chemotherapy, their average age was 33.1 years, the total response rate 100% following induction chemotherapy and the median survival 28.8 (8.0 - 60.0) months. And the 1-, 2- and 3-year overall survival rates were 77.8%, 72.2% and 66.7% respectively. In control patients, the response rate following induction chemotherapy was 100% and the median survival 22.5 (4.0 - 58.0) months. And the 1-, 2- and 3-year overall survival rates were 66.7%, 55.6% and 50.0% respectively. A recent follow-up showed that 5 patients (27.8%) died from relapse in the chemotherapy group and 4 (22.2%) in the control group. The overall deaths were 6 (33.3%) in the chemotherapy group and 9 (50.0%) in the control group. CONCLUSION: Imatinib plus Hyper-CVAD chemotherapy regimen is associated with significantly improved survival rates. Superior to allogeneic hematopoietic stem cell transplantation, it offers a prolonged median response time and survival time in Ph(+)ALL patients.