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

South-to-North, Cross-Disciplinary Training in Global Health Practice: Ten Years of Lessons Learned from an Infectious Disease Field Course in Jamaica

Global commerce, travel, and emerging and resurging infectious diseases have increased awareness of global health threats and opportunities for collaborative and service learning. We review course materials, knowledge archives, data management archives, and student evaluations for the first 10 years of an intensive summer field course in infectious disease epidemiology and surveillance offered in Jamaica. We have trained 300 students from 28 countries through collaboration between the University of the West Indies and U.S. partner universities. Participants were primarily graduate students in public health, but also included health professionals with terminal degrees, and public health nurses and inspectors. Strong institutional synergies, committed faculty, an emphasis on scientific and cultural competencies, and use of team-based field research projects culminate in a unique training environment that provides participants with career-developing experiences. We share lessons learned over the past decade, and conclude that South-to-North leadership is critical in shaping transdisciplinary, cross-cultural, global health practice

South-to-North, Cross-Disciplinary Training in Global Health Practice: Ten Years of Lessons Learned from an Infectious Disease Field Course in Jamaica

Global commerce, travel, and emerging and resurging infectious diseases have increased awareness of global health threats and opportunities for collaborative and service learning. We review course materials, knowledge archives, data management archives, and student evaluations for the first 10 years of an intensive summer field course in infectious disease epidemiology and surveillance offered in Jamaica. We have trained 300 students from 28 countries through collaboration between the University of the West Indies and U.S. partner universities. Participants were primarily graduate students in public health, but also included health professionals with terminal degrees, and public health nurses and inspectors. Strong institutional synergies, committed faculty, an emphasis on scientific and cultural competencies, and use of team-based field research projects culminate in a unique training environment that provides participants with career-developing experiences. We share lessons learned over the past decade, and conclude that South-to-North leadership is critical in shaping transdisciplinary, cross-cultural, global health practice

The Physical Activity Messaging Framework (PAMF) and Checklist (PAMC): International consensus statement and user guide

Effective physical activity messaging plays an important role in the pathway towards changing physical activity behaviour at a population level. The Physical Activity Messaging Framework (PAMF) and Checklist (PAMC) are outputs from a recent modified Delphi study. This sought consensus from an international expert panel on how to aid the creation and evaluation of physical activity messages. In this paper, we (1) present an overview of the various concepts within the PAMF and PAMC, (2) discuss in detail how the PAMF and PAMC can be used to create physical activity messages, plan evaluation of messages, and aid understanding and categorisation of existing messages, and (3) highlight areas for future development and research. If adopted, we propose that the PAMF and PAMC could improve physical activity messaging practice by encouraging evidence-based and target population-focused messages with clearly stated aims and consideration of potential working pathways. They could also enhance the physical activity messaging research base by harmonising key messaging terminologies, improving quality of reporting, and aiding collation and synthesis of the evidence.Education, Faculty ofOther UBCNon UBCKinesiology, School ofReviewedFacultyResearcherOthe

HNRNPC haploinsufficiency affects alternative splicing of intellectual disability-associated genes and causes a neurodevelopmental disorder

Heterogeneous nuclear ribonucleoprotein C (HNRNPC) is an essential, ubiquitously abundant protein involved in mRNA processing. Genetic variants in other members of the HNRNP family have been associated with neurodevelopmental disorders. Here, we describe 13 individuals with global developmental delay, intellectual disability, behavioral abnormalities, and subtle facial dysmorphology with heterozygous HNRNPC germline variants. Five of them bear an identical in-frame deletion of nine amino acids in the extreme C terminus. To study the effect of this recurrent variant as well as HNRNPC haploinsufficiency, we used induced pluripotent stem cells (iPSCs) and fibroblasts obtained from affected individuals. While protein localization and oligomerization were unaffected by the recurrent C-terminal deletion variant, total HNRNPC levels were decreased. Previously, reduced HNRNPC levels have been associated with changes in alternative splicing. Therefore, we performed a meta-analysis on published RNA-seq datasets of three different cell lines to identify a ubiquitous HNRNPC-dependent signature of alternative spliced exons. The identified signature was not only confirmed in fibroblasts obtained from an affected individual but also showed a significant enrichment for genes associated with intellectual disability. Hence, we assessed the effect of decreased and increased levels of HNRNPC on neuronal arborization and neuronal migration and found that either condition affects neuronal function. Taken together, our data indicate that HNRNPC haploinsufficiency affects alternative splicing of multiple intellectual disability-associated genes and that the developing brain is sensitive to aberrant levels of HNRNPC. Hence, our data strongly support the inclusion of HNRNPC to the family of HNRNP-related neurodevelopmental disorders. [Display omitted] We identified genetic variants of HNRNPC in 13 individuals with intellectual disability and global developmental delay. Through a meta-analysis of multiple cell types, we found that loss of HNRNPC affects alternative splicing, in particular of intellectual disability-associated genes. In vivo assays confirmed that neurodevelopment was affected by aberrant HNRNPC levels