Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Rapid and highly variable warming of lake surface waters around the globe

Peer reviewed. ©2015. The Authors.This is an open access article under theterms of the Creative CommonsAttribution-NonCommercial-N oDerivsLicense, which permits use and distri-bution in any medium, provided theoriginal work is properly cited, the use isnon-commerc ial and no modificationsor adaptations are made.In this first worldwide synthesis of in situ and satellite-derived lake data, we find that lake summer surface water temperatures rose rapidly (global mean = 0.34°C decade 1) between 1985 and 2009. Our analyses show that surface water warming rates are dependent on combinations of climate and local characteristics, rather than just lake location, leading to the counterintuitive result that regional consistency in lake warming is the exception, rather than the rule. The most rapidly warming lakes are widely geographically distributed, and their warming is associated with interactions among different climatic factors —from seasonally ice-covered lakes in areas where temperature and solar radiation are increasing while cloud cover is diminishing (0.72°C decade 1) to ice-free lakes experiencing increases in air temperature and solar radiation (0.53°C decade 1). The pervasive and rapid warming observed here signals the urgent need to incorporate climate impacts into vulnerability assessments and adaptation efforts for lakes

Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike’s information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk

Prevention and surveillance of public health risks during extended mass gatherings in rural areas: the experience of the Tamworth Country Music Festival, Australia

Objective: To describe and evaluate the public health response to the Tamworth Country Music Festival, an annual extended mass gathering in rural New South Wales, Australia; and to propose a framework for responding to similar rural mass gatherings.\ud \ud Study design: Process evaluation by direct observation, archival analysis and focus group discussion.\ud \ud Methods: The various components of the public health response to the 2011 Tamworth Country Music Festival were actively recorded. An archival review of documentation from 2007 to 2010 was performed to provide context. A focus group was also conducted to discuss the evolution of the public health response and the consequences of public health involvement.\ud \ud Results: Public health risks increased with increasing duration of the rural mass gathering. Major events held within the rural mass gathering further strained resources. The prevention, preparedness, response and recovery principles provided a useful framework for public health actions. Particular risks included inadequately trained food preparation volunteers functioning in poorly equipped temporary facilities, heat-related ailments and arboviral disease.\ud \ud Conclusion: Extended mass gatherings in rural areas pose particular public health challenges; surge capacity is limited and local infrastructure may be overwhelmed in the event of an acute incident or outbreak. There is value in proactive public health surveillance and monitoring. Annual mass gatherings provide opportunities for continual systems improvement. Early multi-agency planning can identify key risks and identify opportunities for partnership. Special consideration is required for major events within mass gatherings

Composition and ecological drivers of the kwongan scrub and woodlands in the northern Swan Coastal Plain, Western Australia

The nature of community patterns and environmental drivers in kwongan mediterranean‐type shrubland on nutrient‐poor soils occurring in Western Australia remain poorly examined. We aimed to determine whether (i) classification of the kwongan vegetation of the northern Swan Coastal Plain would be ecologically informative and (ii) which environmental drivers underpin the plant community patterns. The study area was positioned on the northern Swan Coastal Plain, locality of Cooljarloo (30°39′ S, 115°22′ E), situated 170 km north of Perth, Western Australia. Compositional (518 species × 337 relevés) and environmental data set (29 variables × 87 relevés) describing time since last fire, soil chemical and physical properties, and terrain characteristics were analysed using classification and ordination techniques. OptimClass assisted in the selection of a robust data transformation, resemblance function and clustering algorithm to identify the vegetation patterns. Major ecological drivers of the vegetation patterns were detected using distance‐based redundancy analysis (db‐RDA). Classification revealed major groupings of Wet Heath and Banksia Woodland distinguishable by the high prevalence of myrtyoid and proteoid taxa, respectively. On floristic‐sociological grounds, we recognised four Wet Heath and two Banksia Woodland communities. The Wet Heath was constrained to areas of higher litter depth (db‐RDA axis 1: 9%). Soil chemical and physical properties explained the highest proportion (17%) of the compositional variance, while the terrain‐ and fire‐related variables explained 2% and <0.001%, respectively. While fire explained little compositional variance overall, a separate db‐RDA analysis found that it may play an important pattern‐structuring role within Banksia Woodlands. Fine‐scale compositional patterns correspond only to a small extent to environmental data; the substantial unexplained variance may be due to slow‐acting neutral and stochastic processes