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.

Louis Nowra, 'Radiance' (Sydney: Currency Press, 1993)

Louis Nowra wrote 'Radiance' especially for the three actors who performed it in the play’s premier season at Belvoir Street Theatre in September 1993. And the Currency Press playscript / programme produced for that season foregrounds these three performers – Rachael Maza, Lydia Miller and Rhoda Roberts – in such a way that the usual distinction between dramatis personae and the actors who play them is considerably diminished. Both the blurb on the back cover and Nowra’s introduction emphasise this special relationship between text and actors, but it is the front cover shot which particularly reflects the conjunction between the two. Rather than depicting a scene from performance, or a ‘graphic’ suggesting something of the play’s thematic content, the front cover of Radiance features the three actors in a posed promotional shot. Arms joined warmly, lovingly, about each other’s waist, bodies turned away from but faces towards the camera, it is the actors we see, not their characters. It’s a very joyful image; they’re positively beaming. Radiant. They look as if they could really be the three half-sisters they portray, except that such moments of blithe sorority are just about non-existent in the play.

'The black hole of our history' : a conversation with Louis Nowra

This is an edited version of an interview recorded for Canadian Theatre Review in 1992. By that time Nowra had established a reputation as one of Australia's foremost playwrights. Part of the generation which succeeded the New Wave of the late 1960s and early 1970s, Nowra became known for a stylistic inventiveness which placed him outside the tradition of realist playwriting in Australia. The international outlook in his early plays, and the fact that he was not exclusively preoccupied with Australian settings and subject matter, was often a focal point in critical accounts of his work. In this interview Nowra discusses his 'internationalism', and a range of topics including the playwriting process; the presence of landscape in his plays; and the autobiographical elements in his work.

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.

Directional dominance on stature and cognition in diverse human populations

Homozygosity has long been associated with rare, often devastating, Mendelian disorders1, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness2. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power3, 4. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10−300, 2.1 × 10−6, 2.5 × 10−10 and 1.8 × 10−10, respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months’ less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples5, 6, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection7, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.