A large-scale exome array analysis of venous thromboembolism
Authors: Lindstrom, Sara; Brody, Jennifer A.; Turman, Constance; Germain, Marine; Bartz, Traci M.; Smith, Erin N.; Chen, Ming-Huei; Puurunen, Marja; Chasman, Daniel; Hassler, Jeffrey; Pankratz, Nathan; Basu, Saonli; Guan, Weihua; Gyorgy, Beata; Ibrahim, Manal; Empana, Jean-Philippe; Olaso, Robert; Jackson, Rebecca; Braekkan, Sigrid K.; McKnight, Barbara; Deleuze, Jean-Francois; O'Donnell, Cristopher J.; Jouven, Xavier; Frazer, Kelly A.; Psary, Bruce M.; Wiggins, Kerri L.; Taylor, Kent; Reiner, Alexander P.; Heckbert, Susan R.; Kooperberg, Charles; Ridker, Paul; Hansen, John-Bjarne; Tang, Weihong; Johnson, Andrew D.; Morange, Pierre-Emmanuel; Tregouet, David A.; Kraft, Peter; Smith, Nicholas L.; Kabrhel, Christopher
Although recent Genome-Wide Association Studies have identified novel associations for common variants, there has been no comprehensive exome-wide search for low-frequency variants that affect the risk of venous thromboembolism (VTE). We conducted a meta-analysis of 11 studies comprising 8,332 cases and 16,087 controls of European ancestry and 382 cases and 1,476 controls of African American ancestry genotyped with the Illumina HumanExome BeadChip. We used the seqMeta package in R to conduct single variant and gene-based rare variant tests. In the single variant analysis, we limited our analysis to the 64,794 variants with at least 40 minor alleles across studies (minor allele frequency [MAF] similar to 0.08%). We confirmed associations with previously identified VTE loci, including ABO, F5, F11, and FGA. After adjusting for multiple testing, we observed no novel significant findings in single variant or gene-based analysis. Given our sample size, we had greater than 80% power to detect minimum odds ratios greater than 1.5 and 1.8 for a single variant with MAF of 0.01 and 0.005, respectively. Larger studies and sequence data may be needed to identify novel low-frequency and rare variants associated with VTE risk.
Patterns of long acting injectable antipsychotic use and associated clinical factors in schizophrenia among 15 Asian countries and region
Authors: Tang, Chao Tian; Chua, Ee Cheong; Chew, Qian Hui; He, Yan-Ling; Si, Tian-Mei; Chiu, Helen F-K; Xiang, Yu-Tao; Kato, Takahiro A.; Kanba, Shigenobu; Shinfuku, Naotaka; Lee, Min-Soo; Park, Seon-Cheol; Park, Yong-Chon; Chong, Mian-Yoon; Lin, Shih-Ku; Yang, Shu-Yu; Tripathi, Adarsh; Avasthi, Ajit; Grover, Sandeep; Kallivayalil, Roy A.; Udomratn, Pichet; Chee, Kok Yoon; Tanra, Andi J.; Rabbani, Md Golam; Javed, Afzal; Kathiarachchi, Samudra; Waas, Dulshika; Myint, Wing Aung; Sartorius, Norman; Van Cuong Tran; Kim Viet Nguyen; Tan, Chay-Hoon; Baldessarini, Ross J.; Sim, Kang
Introduction Patterns of clinical use of long-acting injectable (LAI) antipsychotic drugs in many countries, especially in Asia, for treatment of patients diagnosed with chronic psychotic disorders including schizophrenia are not well established. Methods Within an extensive research consortium, we evaluated prescription rates for first- (FGA) and second-generation antipsychotic (SGA) LAI drugs and their clinical correlates among 3557 subjects diagnosed with schizophrenia across 15 Asian countries and region. Results Overall, an average of 17.9% (638/3557; range: 0.0%-44.9%) of treated subjects were prescribed LAI antipsychotics. Those given LAI vs orally administered agents were significantly older, had multiple hospitalizations, received multiple antipsychotics more often, at 32.4% higher doses, were more likely to manifest disorganized behavior or aggression, had somewhat superior psychosocial functioning and less negative symptoms, but were more likely to be hospitalized, with higher BMI, and more tremor. Being prescribed an FGA vs SGA LAI agent was associated with male sex, aggression, disorganization, hospitalization, multiple antipsychotics, higher doses, with similar risks of adverse neurological or metabolic effects. Rates of use of LAI antipsychotic drugs to treat patients diagnosed with schizophrenia varied by more than 40-fold among Asian countries and given to an average of 17.9% of treated schizophrenia patients. We identified the differences in the clinical profiles and treatment characteristics of patients who were receiving FGA-LAI and SGA-LAI medications. Discussion These findings behoove clinicians to be mindful when evaluating patients' need to be on LAI antipsychotics amidst multifaceted considerations, especially downstream adverse events such as metabolic and extrapyramidal side effects.