New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10−8). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Genetic studies of body mass index yield new insights for obesity biology

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Solutions for archiving data in long-term studies: A reply to Whitlock et al.

In our recent paper [1], we discussed some potential undesirable consequences of public data archiving (PDA) with specific reference to long-term studies and proposed solutions to manage these issues. We reaffirm our commitment to data sharing and collaboration, both of which have been common and fruitful practices supported for many decades by researchers involved in long-term studies. We acknowledge the potential benefits of PDA (e.g., [2]), but believe that several potential negative consequences for science have been underestimated [1] (see also 3 and 4). The objective of our recent paper [1] was to define practices to simultaneously maximize the benefits and minimize the potential unwanted consequences of PDA.

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.

What might GeoHumanities do? Possibilities, practices, publics, and politics

This article draws together seven practitioners and scholars from across the diffuse GeoHumanities community to reflect on the pasts and futures of the GeoHumanities. Far from trying to circle the intellectual wagons around orthodoxies of practice or intent, or to determine possibilities in advance, these contributions and the accompanying commentary seek to create connections across the diverse communities of knowledge and practice that constitute the GeoHumanities. Ahead of these six contributions a commentary situates these discussions within wider concerns with interdisciplinarity and identifies three common themes—possibilities practices, and publics—worthy of further discus- sion and reflection. The introduction concludes by identifying a fourth theme, politics, that coheres these three themes in productive and important ways.

New directions: Air pollution challenges for developing megacities like Delhi

Most major cities around the world experience periods of elevated air pollution levels, which exceed international health-based air quality standards (Kumar et al., 2013). Although it is a global problem, some of the highest air pollution levels are found in rapidly expanding cities in India and China. The sources, emissions, transformations and broad effects of meteorology on air pollution are reasonably well accounted in air quality control strategies in many developed cities; however these key factors remain poorly constrained in the growing cities of countries with emerging economies. We focus here on Delhi, one of the largest global population centres, which faces particular air pollution challenges, now and in the future.

Ethical Values and the Integrity of the Climate Change Regime

This book investigates the ethical values that inform the global carbon integrity system, and reflects on alternative norms that could or should do so. The global carbon integrity system comprises the emerging international architecture being built to respond to the climate change. This architecture can be understood as an 'integrity system'- an inter-related set of institutions, governance arrangements, regulations and practices that work to ensure the system performs its role faithfully and effectively. This volume investigates the ways ethical values impact on where and how the integrity system works, where it fails, and how it can be improved. With a wide array of perspectives across many disciplines, including ethicists, philosophers, lawyers, governance experts and political theorists, the chapters seek to explore the positive values driving the global climate change processes, to offer an understanding of the motivations justifying the creation of the regime and the way that social norms impact upon the operation of the integrity system. The collection focuses on the nexus between ideal ethics and real-world implementation through institutions and laws. The book will be of interest to policy makers, climate change experts, carbon taxation regulators, academics, legal practitioners and researchers.

The pulling power of chocolate: Effects of approach-avoidance training on approach bias and consumption

Previous research has shown that action tendencies to approach alcohol may be modified using computerized ApproacheAvoidance Task (AAT), and that this impacted on subsequent consumption. A recent paper in this journal (Becker, Jostman, Wiers, & Holland, 2015) failed to show significant training effects for food in three studies: Nor did it find effects on subsequent consumption. However, avoidance training to high calorie foods was tested against a control rather than Approach training. The present study used a more comparable paradigm to the alcohol studies. It randomly assigned 90 participants to ‘approach’ or ‘avoid’ chocolate images on the AAT, and then asked them to taste and rate chocolates. A significant interaction of condition and time showed that training to avoid chocolate resulted in faster avoidance responses to chocolate images, compared with training to approach it. Consistent with Becker et al.'s Study 3, no effect was found on amounts of chocolate consumed, although a newly published study in this journal (Schumacher, Kemps, & Tiggemann, 2016) did do so. The collective evidence does not as yet provide solid basis for the application of AAT training to reduction of problematic food consumption, although clinical trials have yet to be conducted.