Genome-wide association study identifies eight loci associated with blood pressure

Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N 71,225 European ancestry, N 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10 24), CYP1A2 (P = 1 × 10 23), FGF5 (P = 1 × 10 21), SH2B3 (P = 3 × 10 18), MTHFR (P = 2 × 10 13), c10orf107 (P = 1 × 10 9), ZNF652 (P = 5 × 10 9) and PLCD3 (P = 1 × 10 8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.

Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1–3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region4, 5, 6, 7, 8, 9, 10, 11. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods—recursive partitioning and regression...

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.

Early childhood profiles of sleep problems and self-regulation predict later school adjustment

Background Children’s sleep problems and self-regulation problems have been independently associated with poorer adjustment to school, but there has been limited exploration of longitudinal early childhood profiles that include both indicators. Aims This study explores the normative developmental pathway for sleep problems and self-regulation across early childhood, and investigates whether departure from the normative pathway is associated with later social-emotional adjustment to school. Sample This study involved 2880 children participating in the Growing Up in Australia: The Longitudinal Study of Australian Children (LSAC) – Infant Cohort from Wave 1 (0-1 years) to Wave 4 (6-7 years). Method Mothers reported on children’s sleep problems, emotional, and attentional self-regulation at three time points from birth to 5 years. Teachers reported on children’s social-emotional adjustment to school at 6-7 years. Latent profile analysis was used to establish person-centred longitudinal profiles. Results Three profiles were found. The normative profile (69%) had consistently average or higher emotional and attentional regulation scores and sleep problems that steadily reduced from birth to 5. The remaining 31% of children were members of two non-normative self-regulation profiles, both characterised by escalating sleep problems across early childhood and below mean self-regulation. Non-normative group membership was associated with higher teacher-reported hyperactivity and emotional problems, and poorer classroom self-regulation and prosocial skills. Conclusion Early childhood profiles of self-regulation that include sleep problems offer a way to identify children at risk of poor school adjustment. Children with escalating early childhood sleep problems should be considered an important target group for school transition interventions.

Improved wound management at lower costs: A sensible goal for Australia

Chronic wounds cost the Australian health system at least US$2·85 billion per year. Wound care services in Australia involve a complex mix of treatment options, health care sectors and funding mechanisms. It is clear that implementation of evidence-based wound care coincides with large health improvements and cost savings, yet the majority of Australians with chronic wounds do not receive evidence-based treatment. High initial treatment costs, inadequate reimbursement, poor financial incentives to invest in optimal care and limitations in clinical skills are major barriers to the adoption of evidence-based wound care. Enhanced education and appropriate financial incentives in primary care will improve uptake of evidence-based practice. Secondary-level wound specialty clinics to fill referral gaps in the community, boosted by appropriate credentialing, will improve access to specialist care. In order to secure funding for better services in a competitive environment, evidence of cost-effectiveness is required. Future effort to generate evidence on the cost-effectiveness of wound management interventions should provide evidence that decision makers find easy to interpret. If this happens, and it will require a large effort of health services research, it could be used to inform future policy and decision-making activities, reduce health care costs and improve patient outcomes.

Untitled (after Steven and John)

'Untitled (after Steven and John)' takes inspiration from Spielbergian tracking shots and Baldessarian collages to create ghostly apparitions that explore the affective power of the cinematic close up. By appropriating and obfuscating this common filmic convention, the work investigates the intersubjective potential of the moving image.

Book Review: "The Interface: IBM and the Transformation of Corporate Design, 1945-1975", John Harwood, Minneapolis: University of Minnesota Press, 2011

Within the history of twentieth-century design, there are a number of well-known objects and stories that are invoked time and time again to capture a pivotal moment or summarize a much broader historical transition. For example, Marcel Breuer’s Model B3 chair is frequently used as a stand-in for the radical investigations of form and new industrial materials occurring at the Bauhaus in the mid-1920s. Similarly, Raymond Loewy’s streamlined pencil sharpener has become historical shorthand for the emergence of modern industrial design in the 1930s. And any discussion of the development of American postwar “organic design” seems incomplete without reference to Charles and Ray Eames’s molded plywood leg splint of 1942. Such objects and narratives are dear to historians of modern design. They are tangible, photogenic subjects that slot nicely into exhibitions, historical surveys, and coffee-table best sellers...

Peace moves: Dance, identity and peacebuilding

Dance is a potential asset for peacebuilding, creating opportunities for nonverbal, embodied learning, exploring identity, and relationships. Peace scholars consider identity and relationships to the ‘other’ as key components in transforming conflict. Focusing on a case study in Mindanao, the Philippines, this paper explores the potential of dance in a peacebuilding context through embodied identity and relationships. In Mindanao, deep-seated cultural prejudices contribute to ongoing conflict entwined with identity. The permeable membrane (Cohen, Gutiérrez & Walker, 2011) is the organising framework describing the constant interaction between artists, facilitators, participants, and communities. It expands peace scholar John Paul Lederach’s concept of the moral imagination, requiring the capacity to envisage one’s self within a web of relationships. In this paper multiple methods of qualitative research including personal interviews are used to further the discussion regarding dance’s potential to diversify the nonverbal tools available for peacebuilding.