The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Meta-Analysis of Gene Level Tests for Rare Variant Association

The vast majority of connections between complex disease and common genetic variants were identified through meta-analysis, a powerful approach that enables large sample sizes while protecting against common artifacts due to population structure, repeated small sample analyses, and/or limitations with sharing individual level data. As the focus of genetic association studies shifts to rare variants, genes and other functional units are becoming the unit of analysis. Here, we propose and evaluate new approaches for performing meta-analysis of rare variant association tests, including burden tests, weighted burden tests, variable threshold tests and tests that allow variants with opposite effects to be grouped together. We show that our approach retains useful features of single variant meta-analytic approaches and demonstrate its utility in a study of blood lipid levels in ∼18,500 individuals genotyped with exome arrays

Number of People Blind or Visually Impaired by Glaucoma Worldwide and in World Regions 1990 – 2010: A Meta-Analysis

Objective: To assess the number of individuals visually impaired or blind due to glaucoma and to examine regional differences and temporal changes in this parameter for the period from 1990 to 2012. Methods: As part of the Global Burden of Diseases (GBD) Study 2010, we performed a systematic literature review for the period from 1980 to 2012. We primarily identified 14,908 relevant manuscripts, out of which 243 high-quality, population-based studies remained after review by an expert panel that involved application of selection criteria that dwelt on population representativeness and clarity of visual acuity methods used. Sixty-six specified the proportion attributable to glaucoma. The software tool DisMod-MR (Disease Modeling–Metaregression) of the GBD was used to calculate fraction of vision impairment due to glaucoma. Results: In 2010, 2.1 million (95% Uncertainty Interval (UI):1.9,2.6) people were blind, and 4.2 (95% UI:3.7,5.8) million were visually impaired due to glaucoma. Glaucoma caused worldwide 6.6% (95% UI:5.9,7.9) of all blindness in 2010 and 2.2% (95% UI:2.0,2.8) of all moderate and severe visual impairment (MSVI). These figures were lower in regions with younger populations (10%). From 1990 to 2010, the number of blind or visually impaired due to glaucoma increased by 0.8 million (95%UI:0.7, 1.1) or 62% and by 2.3 million (95%UI:2.1,3.5) or 83%, respectively. Percentage of global blindness caused by glaucoma increased between 1990 and 2010 from 4.4% (4.0,5.1) to 6.6%. Age-standardized prevalence of glaucoma related blindness and MSVI did not differ markedly between world regions nor between women. Significance: By 2010, one out of 15 blind people was blind due to glaucoma, and one of 45 visually impaired people was visually impaired, highlighting the increasing global burden of glaucoma

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

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Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference