Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

CPAP therapy improves erectile function in patients with severe obstructive sleep apnea

Objectives: Erectile dysfunction (ED) is highly prevalent in obstructive sleep apnea (OSA), however, the effect of continuous positive airway pressure (CPAP) therapy on erectile function has not yet been thoroughly investigated in these patients. Methods: Ninety-four men with severe OSA (ie, with an apnea-hypopnea-index >= 30/h of sleep) were prospectively evaluated for the presence and severity of ED before and after 6-12 months of CPAP therapy. The abbreviated version of the International Index of Erectile Function, (the IIEF-5) was used to rate erectile function. Furthermore, all study participants responded to standard questionnaires of daytime sleepiness (Epworth Sleepiness Scale), quality of life (WHO Wellbeing 5 questionnaire) and depression (Major Depression Inventory). Results: ED as defined by an IIEF-5 score of <= 21 was present in 64 patients (68.1%). CPAP treatment significantly improved erectile function in those patients suffering from moderate and severe ED. Additionally, a trend for a correlation between the improvement of erectile function under CPAP and the hours of its use was observed. Finally, this effect was associated with larger improvements of quality of life in affected patients. Conclusions: ED is very frequent in men with severe OSA and can at least partly be reversed by long-term CPAP therapy in most seriously affected patients. The beneficial effect on erectile function may depend on CPAP compliance and is accompanied by improvements of quality of life. Randomized controlled trials are needed to confirm these findings. (c) 2018 Elsevier B.V. All rights reserved