Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

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

The biomes of Western Australia: A vegetation-based approach using the zonality/ azonality conceptual framework

Vegetation patterns of are the result of environmental drivers operating across a range of ecological and evolutionary scale. Those vegetation patterns at global and continental scales underpin the existence of large-scale functional entities called biomes. Traditionally, terrestrial biomes are recognised and distinguished by way of physiognomic traits thought to reflect the action of selective filters such as climate or disturbance (fire, grazing). This approach is well suited to recognising zonal biomes; it fails, however, to account for the role of other drivers such as soil and hydrology, potentially leading to over simplified representations of the biome patterns in ecologically complex regions such as Western Australia. It is, therefore, of vital importance to consider these patterns and processes and recognise the azonal biomes as well. Using a previously published physiognomic map of the vegetation of Western Australia, we adopted a bottom-up approach to translate the vegetation classification categories into a new biome classification of Western Australia that would more accurately account for the zonal and azonal structures recorded across the landscape. Five continental zonal biomes (Australian Eucalyptus Savanna, Australian Hummock Grassland, Mulga Shrubland, Australian Temperate Woodland, Australian Oceanic Temperate Forest) and one relict biome (Australian Vine Thicket) were identified. We further distinguished 34 types of azonal biomes, including three new ones: argillobiome, duplo-pedobiome and metallobiome. Predictive modelling (using Classification and Regression Trees) was used to define the potential extent of zonal biomes, with the model returning an overall accuracy of 90%. This study shows that a bottom-up approach based on vegetation maps can be used as an effective approximation for defining a robust classification of biome patterns. The predicted zonal biomes correspond well with existing traditional biogeographic classifications, yet some residual climatic discordance warrants further study

The emotional underpinnings of Gardner’s Attitudes and Motivation Test Battery

Book synopsis: This book brings together contributions from the leaders of the language learning motivation field. The varied chapters demonstrate how Gardner's work remains integral to a diverse range of contemporary theoretical issues underlying the psychology of language, even today, 60 years after the publication of Gardner and Lambert's seminal 1959 paper. The chapters cover a wide selection of topics related to applied linguistics, second language acquisition, social psychology, sociology, methodology and historical issues. The book advances thinking on cutting-edge topics in these diverse areas, providing a wealth of information for both students and established scholars that show the continuing and future importance of Gardner and Lambert's ideas

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

Exercise consultation improves short-term adherence to exercise during phase iv cardiac rehabilitation: a randomized controlled trial

This randomized-controlled trial demonstrates that an exercise consultation, based on the transtheoretic model of exercise behavior change, significantly improves short-term adherence to exercise