Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture

The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained

Aerobic fitness as a parameter of importance for labour loss in the heat

Objectives: To derive an empirical model for the impact of aerobic fitness (maximal oxygen consumption; V̇O2max in mL∙kg−1∙min−1) on physical work capacity (PWC) in the heat. Design: Prospective, repeated measures. Methods: Total work completed during 1 h of treadmill walking at a fixed heart rate of 130 b∙min−1 was assessed in 19 young adult males across a variety of warm and hot climate types, characterised by wet-bulb globe temperatures (WBGT) ranging from 12 to 40 °C. For data presentation and obtaining initial parameter estimates for modelling, participants were grouped into low (n = 6, 74 trials), moderate (n = 8, 76 trials), and high (n = 5, 29 trials) fitness, with group mean V̇O2max 42, 52, and 64 mL∙kg−1∙min−1, respectively. For the heated conditions (WBGT 18 to 40 °C), we calculated PWC% by expressing total energy expenditure (kJ above resting) in each trial relative to that achieved in a cool reference condition (WBGT = 12 °C = 100% PWC). Results: The relative reduction in energy expenditure (PWC%) caused by heat was significantly smaller by up to 16% for the fit participants compared to those with lower aerobic capacity. V̇O2max also modulated the relationship between sweat rate and body temperature changes to increasing WBGT. Including individual V̇O2max data in the PWC prediction model increased the predicting power by 4%. Conclusions: Incorporating individual V̇O2max improved the predictive power of the heat stress index WBGT for Physical Work Capacity in the heat. The largest impact of V̇O2max on PWC was observed at a WBGT between 25 and 35 °C. © 2021 Elsevier Lt

Sustainable solutions to mitigate occupational heat strain - An umbrella review of physiological effects and global health perspectives

Background: Climate change is set to exacerbate occupational heat strain, the combined effect of environmental and internal heat stress on the body, threatening human health and wellbeing. Therefore, identifying effective, affordable, feasible and sustainable solutions to mitigate the negative effects on worker health and productivity, is an increasingly urgent need. Objectives: To systematically identify and evaluate methods that mitigate occupational heat strain in order to provide scientific-based guidance for practitioners. Methods: An umbrella review was conducted in biomedical databases employing the following eligibility criteria: 1) ambient temperatures > 28 °C or hypohydrated participants, 2) healthy adults, 3) reported psychophysiological (thermal comfort, heart rate or core temperature) and/or performance (physical or cognitive) outcomes, 4) written in English, and 5) published before November 6, 2019. A second search for original research articles was performed to identify interventions of relevance but lacking systematic reviews. All identified interventions were independently evaluated by all co-authors on four point scales for effectiveness, cost, feasibility and environmental impact. Results: Following screening, 36 systematic reviews fulfilled the inclusion criteria. The most effective solutions at mitigating occupational heat strain were wearing specialized cooling garments, (physiological) heat acclimation, improving aerobic fitness, cold water immersion, and applying ventilation. Although air-conditioning and cooling garments in ideal settings provide best scores for effectiveness, the limited applicability in certain industrial settings, high economic cost and high environmental impact are drawbacks for these solutions. However, (physiological) acclimatization, planned breaks, shading and optimized clothing properties are attractive alternative solutions when economic and ecological sustainability aspects are included in the overall evaluation. Discussion: Choosing the most effective solution or combinations of methods to mitigate occupational heat strain will be scenario-specific. However, this paper provides a framework for integrating effectiveness, cost, feasibility (indoors and outdoor) and ecologic sustainability to provide occupational health and safety professionals with evidence-based guidelines. © 2020 The Author(s)

Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 × 10 -11) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 × 10 -9), ANK3 (rs10994359, P = 2.5 × 10 -8) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 × 10 -9). © 2011 Nature America, Inc. All rights reserved

Copy number variation in obsessive-compulsive disorder and tourette syndrome: A cross-disorder study

Objective Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. Method The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. Results Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p =.09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p =.08 in the current study, p =.025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). Conclusion Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes