Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.This study was funded by the UK Medical Research Council through grants MC_UU_12015/1, MC_PC_13046, MC_PC_13048 and MR/L00002/1. This work was supported by the MRC Metabolic Diseases Unit (MC_UU_12012/5) and the Cambridge NIHR Biomedical Research Centre and EU/EFPIA Innovative Medicines Initiative Joint Undertaking (EMIF grant 115372). Funding for the InterAct project was provided by the EU FP6 program (grant LSHM_CT_2006_037197). This work was funded, in part, through an EFSD Rising Star award to R.A.S. supported by Novo Nordisk. D.B.S. is supported by Wellcome Trust grant 107064. M.I.M. is a Wellcome Trust Senior Investigator and is supported by the following grants from the Wellcome Trust: 090532 and 098381. M.v.d.B. is supported by a Novo Nordisk postdoctoral fellowship run in partnership with the University of Oxford. I.B. is supported by Wellcome Trust grant WT098051. S.O'R. acknowledges funding from the Wellcome Trust (Wellcome Trust Senior Investigator Award 095515/Z/11/Z and Wellcome Trust Strategic Award 100574/Z/12/Z)

Private labels and national brands: a comparison within brand extension

This paper focuses on private labels and manufacturers’ brands; its specific goal is to answer the question whether they are the same in terms of their brand extension effectiveness. The paper reports the results of three experimental studies which analyze the impact of category fit and brand knowledge on brand extension of private label vs. national brands. The results seem to support the view that private labels differ from national brands; contrary to what stated by the branding literature both category fit and brand knowledge, have no significant effect on their extension evaluations

Gotta catch ‘em all: invigorating Pokémon through an innovative brand extension

© 2018 Macmillan Publishers Ltd., part of Springer Nature Despite the success of similar and far more immersive games from lesser known brands, Pokémon Go burst into pop-culture by merging augmented reality technology with the much-adored Pokemon world. The strategy of (re)capturing new and old fans through a highly innovative brand extension has been successful, illustrated by the total distance walked in real life by its players through the game being further than the distance from Earth to Pluto. With the release of further AR gaming extensions from colossal brands already underway (see Star Wars’ Find The Force), how can we explain the success of Pokemon Go as an innovative gaming brand extension? Collecting data from a sample of extensive players of Pokemon Go, results yield intriguing findings into the favourable and unfavourable evaluations of the innovative extension, offering substantial insights to those seeking to expand or rejuvenate brand portfolios through innovative brand extensions

Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies. Nat Genet 2016 Feb; 48(2):189-94

Urbanicity is associated with behavioral and emotional problems in Dutch elementary school-aged children

Adults are 38% more likely to suffer from a psychiatric disorder when they live in an urban compared to a rural area. Urban upbringing may be particularly important. The aim of the present study was to examine whether urbanicity was independently associated with mental health in elementary school-aged children. Specifically, we investigated whether living in a more urban area was associated with exhibiting more behavioral and emotional problems, and whether this remained while controlling for other major risk factors for mental health problems in children. Data came from a Dutch general population study of children (n = 895). Information from four waves was used, in which children were aged approximately 8, 9, 11, and 12 years old. We used mixed effects models to assess the association between urbanicity and the outcomes of behavioral problems and emotional problems separately, while controlling for other major risk factors. The analyses showed that children who lived in more urban areas were significantly more likely to exhibit behavioral (p &lt; .001) and emotional (p &lt; .001) problems. This effect remained when controlling for neighborhood socioeconomic status, gender, ethnicity, family socioeconomic status, parental symptoms of psychopathology, parenting stress, and parenting practices (behavioral: p = .02, emotional: p = .009). In line with research in adults, urbanicity seems to be independently associated with behavioral and emotional problems in children. A possible underlying mechanism is that the city is a stressful environment for children to grow up in, which contributes to an increased risk for mental health problems.Funding Agency:Netherlands Organization for Health Research and Development 26200002 120620029</p