FTO genotype is associated with phenotypic variability of body mass index

There is evidence across several species for genetic control of phenotypic variation of complex traits1, 2, 3, 4, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ~170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)5, 6, 7, is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ~0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation9, 10. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

Tombstone of Clara Meyer nee Benjamin; Strangriede Cemetery, Hannover Cemeteries; Tombs

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International contact lens prescribing in 2014

Since the late 1990s, the International Contact Lens Prescribing Survey Consortium has prospectively gathered information about 285,000 contact lens fits from more than 50 countries. This article presents our 14th annual summary of current trends published in Contact Lens Spectrum. With only minor differences in the distribution of our surveys among markets, we have continued to adopt the same approach throughout the past 18 years. Through national coordinators, we approach contact lens prescribers in each country and ask them to record information about the first 10 patients whom they fit with contact lenses after receipt of our survey form. The information collected is generic, and respondents are weighted to reflect the volume of contact lens fits undertaken by each. For this 2014 report, we present information about 25,179 contact lens fits from 32 countries...

International contact lens prescribing in 2015

We have been collecting data on worldwide contact lens prescribing habits for almost 20 years. Over this time period, we have amassed prospective information about 315,000 contact lens fits in 59 countries. This article marks our 15th report in Contact Lens Spectrum and features a breakdown of more than 23,000 contact lens fits in 34 markets. As in previous years, our international network of coordinators distributed survey forms to eyecare practitioners in their market who then recorded generic information about the first 10 patients fit with contact lenses after receipt. Information is gathered about patient age and gender; whether the contact lenses are prescribed as a new fit or a refit; contact lens material, design, and replacement frequency; number of intended days per week of use; wearing modality; and care system. Contact lens fits are weighted to reflect the number of fits undertaken by each eyecare practitioner. The study data were entered and processed at the University of Manchester and at the University of Waterloo.

Global Media and National Policies : The Return of the State

Conventional wisdom views globalization as a process that heralds the diminishing role or even 'death' of the state and the rise of transnational media and transnational consumption, that defy state control or regulation. This book questions these assumptions and shows that the nation-state never left and is still a force to be reckoned with.

National media regulations in an age of convergent media: Beyond globalisation, neo-liberalism and internet freedom theories

There is a widely held view that the nation-state has become less central to media and communications policy over the last two decades. As Jan van Cuilenberg and Denis McQuail (2003, p. 181) observed in their overview of trends in communications policy-making, 'the old normative media policies have been challenged and policy-makers are searching for a new communications policy paradigm'. There are characteristically five factors put forward as to why the nation-state has become less central to media in the twenty-first century

Accountability for good faith in commercial dealing: The Carter v Boehm legacy 250 years on

In common law jurisdictions such as England, Australia, Canada and New Zealand good faith in contracting has long been recognised in specific areas of the law such as insurance law and franchising, and more recently the implied duties of good faith and mutual trust and convenience in employment contracts have generated a considerable volume of case law. Outside of these areas of law that may be characterised as being strongly‘relational’ in character,the courts in common law jurisdictions have been reluctant to embrace a more universal application of good faith in contracting and performance. However increasingly there are cases which support the proposition that there is a common law duty of good faith of general application to all commercial contracts. Most important in this context is the recent decision of the Supreme Court of Canada in Bhasin v Hrynew.1 However, this matter is by no means resolved in all common law jurisdictions. This article looks at the recent case law and literature and at various legislative incursions including statutes, codes of conduct and regulations impacting good faith in commercial dealings.

Evaluación del potencial agro-ecoturístico en la finca Jardín del Edén, comunidad Las Azucenas, San Carlos, Río San Juan, Nicaragua

El agroecoturismo es la combinación de dos actividades turísticas en donde se ofrece la posibilidad de conocer los aspectos culturales, prácticas tradicionales de cultivos, como también promover la conservación y disfrutar de los parajes naturales. El estudio se llevó a cabo en una finca privada, propiedad del señor Patricio Maradiaga ubicada en la comunidad Las Azucenas, a 13 km de la ciudad de San Carlos, Rio San Juan. El área de estudio abarca 60mz. Se llevó a cabo el estudio en tres etapas de campo utilizando un formato de diagnóstico y reconocimiento de los sitios de interés, combinando las entrevistas que se le realizaron al dueño de la finca al igual que a turistas extranjeros y nacionales. Dentro de los atractivos encontrados se destacaron, belleza escénica, bosque húmedo tropical y avistamiento de aves. Con base en la información recopilada, se elaboró la propuesta de un circuito agroecoturístico con 3 opciones de recorrido y la presentación de un paquete agroecoturístico con el debido costo, se elaboró una propuesta de mejora para atención al cliente tomando en cuenta las facilidades, condiciones y necesidades de la finca en estudio. Se espera que al implementar el circuito agroecoturístico se mejore la calidad de vida del productor y se promueva la conservación de la fauna que habita en el bosque. Ante el posible efecto que tenga el agroecoturismo sobre las especies silvestres, se recomienda no utilizar objetos que produzcan ruido u olores que perturben su ciclo reproductivo.

Sea turtles in Florida's Atlantic waters

Management of marine turtles presents various challenges due to their highly migratory nature, which includes major ontogenetic habitat shifts, seasonal movements between feeding grounds, and migrations to and from breeding grounds. Further, sea turtle spatial distributions often differ in species-specific ways during similar temporal periods. Various approaches combine to give valuable insights into spatial and temporal distributions of sea turtles and provide critical knowledge for understanding and protecting these imperiled species. Here we summarize and synthesize available data that document sea turtle occurrences in waters from the Florida Straits (lat. 24°28´N) north to the latitude of Jacksonville, Fla. (lat. 30°20´ N), including waters up to 150 km offshore, termed Florida’s Atlantic waters for this review. We summarize 951 satellite tracked sea turtles, 288 of which crossed into Florida’s Atlantic waters. All species of sea turtles inhabiting the Atlantic Ocean were found to use Florida Atlantic waters. Sea turtles use Florida’s Atlantic waters year-round, yet distributions of individual species vary seasonally. We provide a current synthesis describing the spatial and temporal distributions of the five sea turtles species using Florida’s Atlantic waters and suggest areas where further study may be warranted.

B Cell Activation in Insulin Resistance and Obesity

Our group has demonstrated that inflammatory diseases such as type 2 diabetes (DM), inflammatory bowel disease (IBD), and periodontal disease (PD) are associated with altered B cell function that may contribute to disease pathogenesis. B cells were found to be highly activated with characteristics of inflammatory cells. Obesity is a pre-disease state for cardiovascular disease and type 2 diabetes and is considered a state of chronic inflammation. Therefore, we sought to better characterize B cell function and phenotype in obese patients. We demonstrate that (Toll-like receptor) TLR4 and CD36 expression by B cells is elevated in obese subjects, suggesting increased sensing of lipopolysaccharide (LPS) and other TLR ligands. These ligands may be of microbial, from translocation from a leaky gut, or host origin. To better assess microbial ligand burden and host response in the bloodstream, we measured LPS binding protein (LBP), bacterial/permeability increasing protein (BPI), and high mobility group box 1 (HMGB1). Thus far, our data demonstrate an increase in LBP in DM and obesity indicating increased responses to TLR ligands in the blood. Interestingly, B cells responded to certain types of LPS by phosphorylating extracellular-signal-regulated kinases (ERK) 1/2. A better understanding of the immunological state of obesity and the microbial and endogenous TLR ligands that may be activating B cells will help identify novel therapeutics to reduce the risk of more dangerous conditions, such as cardiovascular disease.

Plasma HDL cholesterol and risk of myocardial infarction: A mendelian randomisation study

Background: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian random isation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.
Methods: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20 913 myocardial infarction cases, 95 407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12 482 cases of myocardial infarction and 41 331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.
Findings: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher p=8×10-13) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with noncarriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13 95% CI 1·69-2·69, p=2×10 -10).
Interpretation: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.

Genetic Markers Enhance Coronary Risk Prediction in Men: The MORGAM Prospective Cohorts

Background: More accurate coronary heart disease (CHD) prediction, specifically in middle-aged men, is needed to reduce the burden of disease more effectively. We hypothesised that a multilocus genetic risk score could refine CHD prediction beyond classic risk scores and obtain more precise risk estimates using a prospective cohort design.

Methods: Using data from nine prospective European cohorts, including 26,221 men, we selected in a case-cohort setting 4,818 healthy men at baseline, and used Cox proportional hazards models to examine associations between CHD and risk scores based on genetic variants representing 13 genomic regions. Over follow-up (range: 5-18 years), 1,736 incident CHD events occurred. Genetic risk scores were validated in men with at least 10 years of follow-up (632 cases, 1361 non-cases). Genetic risk score 1 (GRS1) combined 11 SNPs and two haplotypes, with effect estimates from previous genome-wide association studies. GRS2 combined 11 SNPs plus 4 SNPs from the haplotypes with coefficients estimated from these prospective cohorts using 10-fold cross-validation. Scores were added to a model adjusted for classic risk factors comprising the Framingham risk score and 10-year risks were derived.

Results: Both scores improved net reclassification (NRI) over the Framingham score (7.5%, p = 0.017 for GRS1, 6.5%, p = 0.044 for GRS2) but GRS2 also improved discrimination (c-index improvement 1.11%, p = 0.048). Subgroup analysis on men aged 50-59 (436 cases, 603 non-cases) improved net reclassification for GRS1 (13.8%) and GRS2 (12.5%). Net reclassification improvement remained significant for both scores when family history of CHD was added to the baseline model for this male subgroup improving prediction of early onset CHD events.

Conclusions: Genetic risk scores add precision to risk estimates for CHD and improve prediction beyond classic risk factors, particularly for middle aged men.