Associations of early adulthood life transitions with changes in fast food intake: a latent trajectory analysis

Abstract: Background: Early adulthood is a period of rapid personal development when individuals experience major life transitions (e.g. leaving the parental home, leaving education, beginning employment, cohabitation and parenthood). Changes in social and physical environments associated with these transitions may influence development of health-related behaviours. Consumption of fast food is one behaviour associated with poor diet and long-term health outcomes. In this study we assess how frequency of fast food consumption changes across early adulthood, and how major life transitions are associated with changes in fast food intake. Methods: Data were collected across four waves of the Project EAT study, from mean age 14.9 (SD = 1.6) to mean age 31.1 (SD = 1.6) years. Participants reporting data at two or more waves were included (n = 2902). Participants reported past week frequency of eating food from a fast food restaurant and responded to questions on living arrangements, education and employment participation, and having children. To assess changes in fast food we developed a latent growth model incorporating an underlying trajectory of fast food intake, five life transitions, and time-invariant covariates. Results: Mean fast food intake followed an underlying quadratic trajectory, increasing through adolescence to a maximum of 1.88 (SE 0.94) times/week and then decreasing again through early adulthood to 0.76 (SE 2.06) times/week at wave 4. Beginning full-time employment and becoming a parent both contributed to increases in fast food intake, each resulting in an average increase in weekly fast food intake of 0.16 (p < 0.01) times/week. Analysis of changes between pairs of waves revealed stronger associations for these two transitions between waves 1–2 (mean age 14.9–19.4 years) than seen in later waves. Leaving the parental home and beginning cohabitation were associated with decreases in fast food intake of − 0.17 (p = 0.004) and − 0.16 (p = 0.007) times/week respectively, while leaving full-time education was not associated with any change. Conclusions: The transitions of beginning full-time employment and becoming a parent were associated with increases in fast food intake. Public health policy or interventions designed to reduce fast food intake in young adults may benefit from particular focus on populations experiencing these transitions, to ameliorate their impact

Spermine Binding to Parkinson’s Protein α-Synuclein and Its Disease-Related A30P and A53T Mutants

Aggregation of α-synuclein (α-syn), a protein implicated in Parkinson’s disease (PD), is believed to progress through formation of a partially folded intermediate. Using nanoelectrospray ionization (nano-ESI) mass spectrometry combined with ion mobility measurements we found evidence for a highly compact partially folded family of structures for α-syn and its disease-related A53T mutant with net charges of −6, −7, and −8. For the other early onset PD mutant, A30P, this highly compact population was only evident when the protein had a net charge of −6. When bound to spermine near physiologic pH, all three proteins underwent a charge reduction from the favored solution charge state of −10 to a net charge of −6. This charge reduction is accompanied by a dramatic size reduction of about a factor of 2 (cross section of 2600 Å^2 (−10 charge state) down to 1430 Å^2 (−6 charge state)). We conclude that spermine increases the aggregation rate of α-syn by inducing a collapsed conformation, which then proceeds to form aggregates

Intended Consequences Statement in Conservation Science and Practice

As the biodiversity crisis accelerates, the stakes are higher for threatened plants and animals. Rebuilding the health of our planet will require addressing underlying threats at many scales, including habitat loss and climate change. Conservation interventions such as habitat protection, management, restoration, predator control, trans location, genetic rescue, and biological control have the potential to help threatened or endangered species avert extinction. These existing, well-tested methods can be complemented and augmented by more frequent and faster adoption of new technologies, such as powerful new genetic tools. In addition, synthetic biology might offer solutions to currently intractable conservation problems. We believe that conservation needs to be bold and clear-eyed in this moment of great urgency

Genome-Wide Screen of Three Herpesviruses for Protein Subcellular Localization and Alteration of PML Nuclear Bodies

Herpesviruses are large, ubiquitous DNA viruses with complex host interactions, yet many of the proteins encoded by these viruses have not been functionally characterized. As a first step in functional characterization, we determined the subcellular localization of 234 epitope-tagged proteins from herpes simplex virus, cytomegalovirus, and Epstein–Barr virus. Twenty-four of the 93 proteins with nuclear localization formed subnuclear structures. Twelve of these localized to the nucleolus, and five at least partially localized with promyelocytic leukemia (PML) bodies, which are known to suppress viral lytic infection. In addition, two proteins disrupted Cajal bodies, and 19 of the nuclear proteins significantly decreased the number of PML bodies per cell, including six that were shown to be SUMO-modified. These results have provided the first functional insights into over 120 previously unstudied proteins and suggest that herpesviruses employ multiple strategies for manipulating nuclear bodies that control key cellular processes

Rare and low-frequency coding variants alter human adult height

Height is a highly heritable, classic polygenic trait with ~700 common associated variants identified so far through genome - wide association studies . Here , we report 83 height - associated coding variants with lower minor allele frequenc ies ( range of 0.1 - 4.8% ) and effects of up to 2 16 cm /allele ( e.g. in IHH , STC2 , AR and CRISPLD2 ) , >10 times the average effect of common variants . In functional follow - up studies, rare height - increasing alleles of STC2 (+1 - 2 cm/allele) compromise d proteolytic inhibition of PAPP - A and increased cleavage of IGFBP - 4 in vitro , resulting in higher bioavailability of insulin - like growth factors . The se 83 height - associated variants overlap genes mutated in monogenic growth disorders and highlight new biological candidates ( e.g. ADAMTS3, IL11RA, NOX4 ) and pathways ( e.g . proteoglycan/ glycosaminoglycan synthesis ) involved in growth . Our results demonstrate that sufficiently large sample sizes can uncover rare and low - frequency variants of moderate to large effect associated with polygenic human phenotypes , and that these variants implicate relevant genes and pathways

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape

Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways

GA4GH: International policies and standards for data sharing across genomic research and healthcare.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits

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