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.

On medium specificity and discipline crossovers in modern art : An interview with Jacques Ranciére on Medium-Specificity and Discipline Crossovers in Modern Art

Jacques Ranciere's work on aesthetics has received a great deal of attention recently. Given his work has enormous range – taking in art and literature, political theory, historiography, pedagogy and worker's history – Andrew McNamara and Toni Ross (UNSW) seek to explore his wider project in this interview, while showing how it leads to his alternative insights into aesthetics. Rancière sets aside the core suppositions linking the medium to aesthetic judgment, which has informed many definitions of modernism. Rancière is emphatic in freeing aesthetic judgment from issues of medium-specificity. He argues that the idea of autonomy associated with medium-specificity – or 'truth to the medium' – was 'a very late one' in modernism, and that post-medium trends were already evident in early modernism. While not stressing a simple continuity between early modernism and contemporary art, Ranciere nonetheless emphasizes the ethical and political ramifications of maintaining an a-disciplinary stance.

Joseph A. Schumpeter, capitalism, socialism, and democracy

This is a review of "Capitalism, socialism, and democracy", by Joseph A. Schumpeter, New York, Harper Perennial, 1942 (first Harper Colophon edition published 1975). "The public mind has by now so thoroughly grown out of humor with it as to make condemnation of capitalism and all its works a foregone conclusion – almost a requirement of the etiquette of discussion. Whatever his political preference, every writer or speaker hastens to conform to this code and to emphasize his critical attitude, his freedom from ‘complacency’, his belief in the inadequacies of capitalist achievement, his aversion to capitalist and his sympathy with anti-capitalist interests. Any other attitude is voted not only foolish but anti-social and is looked upon as an indication of immoral servitude." We might easily mistake this for a voice weary of contemplating the implications for neo-liberal nostrums of our current global financial crisis were it not for the rather formal, slightly arch, style and the gender exclusive language. It was in fact penned in the depths of World War II by Harvard economist Joseph Schumpeter, who fell off the map only to re-emerge from the 1970s as oil shocks and stagflation in the west presaged the decline of the Keynesian settlement, as east Asian newly industrialising economies were modelling on his insistence that entrepreneurialism, access to credit and trade were the pillars of economic growth, and as innovation became more of a watchword for post-industrial economies in general. The second coming was perhaps affirmed when his work was dubbed by Forbes in 1983 – on the occasion of the 100th anniversary of the birth of both men – as of greater explanatory import than Keynes’. (And what of our present resurgent Keynesian moment?)...

Wrapped fragments : Drapery, the eighteenth century portrait bust and the male subject

The depiction of drapery (generalised cloth as opposed to clothing) is a well-established convention of Neo-Classical sculpture and is often downplayed by art historians as of purely rhetorical value. It can be argued however that sculpted drapery has served a spectrum of expressive ends, the variety and complexity of which are well illustrated by a study of its use in portrait sculpture. For the Neo-Classical portrait bust, drapery had substantial iconographic and political meaning, signifying the new Enlightenment notions of masculine authority. Within the portrait bust, drapery also served highly strategic aesthetic purposes, alleviating the abruptness of the truncated format and the compromising visual consequences of the “cropped” body. With reference to Joseph Nollekens’ portraits of English statesman Charles James Fox and the author’s own sculptural practice, this paper analyses the Neo-Classical use of drapery to propose that rendered fabric, far from mere stylistic flourish, is a highly charged visual signifier with much scope for exploration in contemporary sculptural practice.

Stripping Sight Bare : Alison Jones’ ‘Portraits by Proxy’

In this paper I analyse UK artist Alison Jones’ sonic interventions Portrait of the Artist by Proxy (2008), Voyeurism by Proxy (2008) and Art, Lies and Audio Tapes (2009). In Portrait of the Artist by Proxy, Jones – who, due to deteriorating vision, has not seen her reflection in a mirror in years – asks and trusts participants to audio-describe her own image back to her. In Voyeurism by Proxy, Jones asks participants to audio-describe erotic drawings by Gustav Klimt. In Art, Lies and Audio Tapes, Jones asks participants to audio-describe other artworks, such as W.F. Yeames’ And When Did You Last see Your Father?. In these portraits by proxy, Jones opens her image, and other images, to interpretation. In doing so, Jones draws attention to the way sight is privileged as a mode of access to fixed, fundamental truths in Western culture – a mode assumed to be untainted by filters that skew perception of the object. “In a culture where vision is by far the dominant sense,” Jones says, “and as a visual artist with a visual impairment, I am reliant on audio-description …Inevitably, there are limitations imposed by language, time and the interpreter’s background knowledge of the subject viewed, as well as their personal bias of what is deemed important to impart in their description” . In these works, Jones strips these background knowledges, biases and assumptions bare. She reveals different perceptions, as well as tendencies or censor, edit or exaggerate descriptions. In this paper, I investigate how, by revealing unconscious biases, Jones’ works renders herself and her participants vulnerable to a change of perception. I also examine how Jones’ later editing of the audio-descriptions allows her to show the instabilities of sight, and, in Portrait of the Artist by Proxy, to reclaim authorship of her own image.

Stephen Russell : Super Vanitas

This article is an analysis and contextualisation of 'Super Vanitas' a video installation by Stephen Russell that was held at Boxcopy ARI, Brisbane. It discusses the significance of the painting 'Death of Marat' (J.L. David, 1793) to the work and describes the methodological processes that are revealed in the work.

An interview with Jacques Rancière : on medium-specificity and discipline crossovers in modern art

Jacques Rancière's work on aesthetics has received a great deal of attention in recent years. Given his work has enormous range – covering art and literature, political theory, historiography, pedagogy and worker's history – Andrew McNamara and Toni Ross (UNSW) explore his wider critical ambitions in this interview, while showing how it leads to alternative insights into aesthetics. Rancière sets aside the core suppositions linking the medium to aesthetic judgment, which has informed many definitions of modernism. Rancière is emphatic in freeing aesthetic judgment from issues of medium-specificity. He argues that the idea of autonomy associated with medium-specificity – or 'truth to the medium' – was 'a very late one' in modernism, and that post-medium trends were already evident in early modernism. While not stressing a simple continuity between early modernism and contemporary art, Ranciere nonetheless emphasizes the on-going ethical and political ramifications of maintaining an a-disciplinary stance.

Joseph Maiden and the national and transnational circulation of Wattle Acacia spp

During the nineteenth century and in the early years of the twentieth century wattle was circulated by botanists, botanical institutions, interested individuals, commercial seedsmen and government authorities. Wattle bark was used in the production of leather and was the subject of debate regarding its commercial development and conservation in Australia. It was also trialled in many other locations including America, New Zealand, Hawaii and Russia. In the process, South Africa became a major producer of wattle bark for a global market. At the same time wattle was also promoted as a symbol of Australian nationalism. This paper considers this movement of wattles, wattle material and wattle information by examining the career of one active agent in these botanical transfers: Joseph Maiden. In doing so it demonstrates that these seemingly different uses of the wattle overlap transnational and national spheres.

Maiden, Joseph

Joseph Henry Maiden was born in London in 1859 and sailed for Australia in 1880, where he lived for the remainder of his life. He was an ardent Australian nationalist, and like many immigrants of this time, remained proud of his British heritage. His sweetheart, Eliza Jane Hammond, followed him to Australia in 1883. They married in Kew the day after she made port in Melbourne, and together in Sydney they raised five children. [1] During the first phase of his career Maiden presided over the Technological Museum of Sydney from 1882 to 1896. In the second phase, he was the director of the Sydney Botanic Gardens from 1896 to 1924. There he managed a whole complex of parks including the Domain,Centennial Park and the Governor's residences, a state nursery at Campbelltown and a scientific institution, the National Herbarium of New South Wales, devoted to botany. A short time after his retirement, he died at his home in Turramurra in 1925...

Activism, art and social practice : a case study using Jacques Ranciere’s framework for analysis

The question can no longer just be whether “art and social practice” or creative forms of activism are part of larger neo liberal agenda nor if they are potentially radical in their conception, delivery or consumption. The question also becomes: what are the effects of social practice art and design for the artists, institutions, and the publics they elicit in public and private spaces; that is, how can we consider such artworks differently? I argue the dilution of social practices’ potentially radical interventions into cultural processes and their absorption into larger neo liberal agendas limits how, as Jacques Rancière might argue, they can intervene in the “distribution of the sensible.” I will use a case study example from The Center for Tactical Magic, an artist group from the San Francisco Bay Area.

Corrigendum to "Mapping hippocampal and ventricular change in Alzheimer disease" [NeuroImage 22 (2004) 1754-1766] (DOI:10.1016/j.neuroimage.2004.03.040)

We recently noticed an error in the demographic data in this article. The validity of the findings and the conclusions of the paper is not affected. However, there is an error in the reported sample size and in the means and standard deviations of the subjects’ ages and MMSE scores. We would like to correct this error, which came to light when we were re-analyzing the data for a meta-analysis. The error occurred because an older version of a spreadsheet was incorrectly used when reporting the sample composition. Instead of examining 12 Alzheimer's disease patients and 14 healthy elderly controls, we in fact examined 17 Alzheimer’s disease patients and 14 healthy elderly controls. All maps and morphometric data reported in the paper are correct, except that the sample size was in fact slightly higher than that originally reported, and the maps computed in the paper were based on the larger sample (which included five more subjects in the Alzheimer’s disease group). All of the maps and figures in the paper are correct, and the conclusions of the paper are unchanged. We apologize for this error, which falls under the sole responsibility of the first author. The corrected demographic information appears below.

Global, regional, and national disability-adjusted life years (DALYs) for 306 diseases and injuries and healthy life expectancy (HALE) for 188 countries, 1990–2013: Quantifying the epidemiological transition

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age–sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development. Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time. Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6·2 years (95% UI 5·6–6·6), from 65·3 years (65·0–65·6) in 1990 to 71·5 years (71·0–71·9) in 2013, HALE at birth rose by 5·4 years (4·9–5·8), from 56·9 years (54·5–59·1) to 62·3 years (59·7–64·8), total DALYs fell by 3·6% (0·3–7·4), and age-standardised DALY rates per 100 000 people fell by 26·7% (24·6–29·1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non–communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries. Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition—in which increasing sociodemographic status brings structured change in disease burden—is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

Background The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. Methods Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk–outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990–2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. Findings All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8–58·5) of deaths and 41·6% (40·1–43·0) of DALYs. Risks quantified account for 87·9% (86·5–89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. Interpretation Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

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.