Whole-genome sequencing analysis of clozapine-induced myocarditis.

One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (p < 0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.

Rates and risks of injury during intercollegiate basketball.

BACKGROUND: Previous studies of basketball injury have not been able to assess injury incidence and risk. PURPOSE: To determine rates and risks of injury in Canadian intercollegiate basketball. STUDY DESIGN: Prospective cohort study. METHODS: Standardized data were collected with a validated instrument from 98.1% of the 318 athletes on the eight men's basketball teams in the Canada West Division of the Canadian Intercollegiate Athletic Union. RESULTS: A total of 142 athletes sustained 215 injuries (44.7% of players injured) over the 2-year study period. The greatest number of injuries resulting in more than seven sessions of time loss involved the knee, whereas the most common injuries causing fewer than seven sessions of time loss involved the ankle. The most common mechanism of injury was contact with another player, especially in the "key." Injuries occurred 3.7 times more often in games than during practice. Centers had the highest rate of injury, followed by guards, and then forwards. The relative risk of reinjury was significantly increased by previous injuries to the elbow, shoulder, knee, hand, lower spine or pelvis, and by concussions. CONCLUSIONS: Risk factors for injury were previous injury, games as opposed to practice, player position, player contact, and court location.