Socioeconomic Position, Stress, and Cortisol in Relation to Waist Circumference in African American and White Women

Objective—Abdominal fat deposition has been shown to be related to hypertension, dyslipidemia and diabetes. Studies have shown a correlation between cortisol (a stress hormone) and abdominal fat deposition. Low socioeconomic position (SEP) has also been shown to be related to abdominal fat deposition. It is hypothesized that chronic stress associated with low SEP leads to high cortisol levels which in turn lead to abdominal fat deposition. Previous research in this area has included mainly European subjects. The purpose of this study was to examine the evidence for the SEP-chronic stress-cortisol-abdominal fat hypothesis in a sample of African American and White American women. Design—Data from the Regional Assessment Health Surveillance Study (RAHSS), a survey and physical examination of a representative sample of African American and White adults residing in six counties in Georgia, were utilized. The study population included 111 African American and 119 White women. Abdominal fat deposition was measured by waist circumference (inches). Education and income were the measures of SEP. Other exposures examined included serum cortisol, self-reported daily stress level, cigarette smoking, marital status, and number of children. Associations were examined using multiple linear regression models adjusted for age and body mass index (BMI). Results—Among White women, less-educated women had a waist circumference 2.22 inches larger (P<.05) than more highly educated women. Among African American women, separated or divorced women (+2.29 in, P<.05) and widowed women (+3.13 in, P<.01) had larger waist circumferences than married women. No other factors were significantly associated with waist circumference. Conclusions—The SEP-chronic stress abdominal fat accumulation hypothesis was only partially supported by the data. Different stressors and pathways may be important in producing abdominal fat accumulation in African American and White women

Implementation of U.K. Earth system models for CMIP6

We describe the scientific and technical implementation of two models for a core set of experiments contributing to the sixth phase of the Coupled Model Intercomparison Project (CMIP6). The models used are the physical atmosphere-land-ocean-sea ice model HadGEM3-GC3.1 and the Earth system model UKESM1 which adds a carbon-nitrogen cycle and atmospheric chemistry to HadGEM3-GC3.1. The model results are constrained by the external boundary conditions (forcing data) and initial conditions.We outline the scientific rationale and assumptions made in specifying these. Notable details of the implementation include an ozone redistribution scheme for prescribed ozone simulations (HadGEM3-GC3.1) to avoid inconsistencies with the model's thermal tropopause, and land use change in dynamic vegetation simulations (UKESM1) whose influence will be subject to potential biases in the simulation of background natural vegetation.We discuss the implications of these decisions for interpretation of the simulation results. These simulations are expensive in terms of human and CPU resources and will underpin many further experiments; we describe some of the technical steps taken to ensure their scientific robustness and reproducibility

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions