Previously described methods of analysis allow variants in a gene to be weighted more highly according to rarity and/or predicted function and then for the variant contributions to be summed into a ...gene-wise risk score, which can be compared between cases and controls using a t-test. However, this does not allow incorporating covariates into the analysis. Schizophrenia is an example of an illness where there is evidence that different kinds of genetic variation can contribute to risk, including common variants contributing to a polygenic risk score (PRS), very rare copy number variants (CNVs) and sequence variants. A logistic regression approach has been implemented to compare the gene-wise risk scores between cases and controls, while incorporating as covariates population principal components, the PRS and the presence of pathogenic CNVs and sequence variants. A likelihood ratio test is performed, comparing the likelihoods of logistic regression models with and without this score. The method was applied to an ethnically heterogeneous exome-sequenced sample of 6000 controls and 5000 schizophrenia cases. In the raw analysis, the test statistic is inflated but inclusion of principal components satisfactorily controls for this. In this dataset, the inclusion of the PRS and effect from CNVs and sequence variants had only small effects. The set of genes which are FMRP targets showed some evidence for enrichment of rare, functional variants among cases (p = 0.0005). This approach can be applied to any disease in which different kinds of genetic and non-genetic risk factors make contributions to risk.
A number of theories have been put forward regarding the nature of the factors driving selection for LP as a trait which would allow adults to consume milk, allowing them to benefit from factors such ...as intake of calories, protein, vitamin D or simply pathogen-free fluid, 2. ...there is no evidence that LNP status has any large influence on milk consumption nor that it has serious effects on health. Subsequently they state that LP individuals will derive approximately twice as many calories from lactose as LNP individuals but say that this difference is "not that high". ...while they do note that specific calorific benefits are conferred by LP they do not see this as potentially conferring an evolutionary advantage, with a consequence being that contemporary researchers fail to even consider this possibility 3. ...the specific calorific benefits conferred by LP do appear to be substantial.
Assay of Transposase Accessible Chromatin sequencing (ATAC-seq) is widely used in studying chromatin biology, but a comprehensive review of the analysis tools has not been completed yet. Here, we ...discuss the major steps in ATAC-seq data analysis, including pre-analysis (quality check and alignment), core analysis (peak calling), and advanced analysis (peak differential analysis and annotation, motif enrichment, footprinting, and nucleosome position analysis). We also review the reconstruction of transcriptional regulatory networks with multiomics data and highlight the current challenges of each step. Finally, we describe the potential of single-cell ATAC-seq and highlight the necessity of developing ATAC-seq specific analysis tools to obtain biologically meaningful insights.
Genetic variants causing diseases with hypertension as a secondary feature have previously been identified. Studies focussing on primary hypertension have utilised common and latterly rare genetic ...variants in attempts to elucidate the genetic contribution to the risk of primary hypertension.
Using genome-wide association studies (GWASs), associations of hypertension with hundreds of common genetic variants have been reported, implicating thousands of genes. Individual variants have small effect sizes and cumulatively account for around 6% of genetic risk. The common variant signal is enriched for relevant tissues and physiological processes, while some variants are associated with traits expected to have secondary impacts on hypertension risk, such as fruit intake, BMI, or time watching television. Studies using rare variants obtained from exome sequence data have implicated a small number of genes for which impaired function has moderate effects on blood pressure and/or hypertension risk. Notably, genetic variants which impair elements of guanylate cyclase activation, stimulated by either natriuretic hormones or nitric oxide, increase hypertension risk. Conversely, variants impairing dopamine beta-hydroxylase or renin production are associated with lower blood pressure. Variants for which a definite effect can be designated remain cumulatively extremely rare and again make only a small contribution to overall genetic risk. Although these results are of interest, it is not clear that they provide radical new insights or identify drug targets which were not previously known. Nor does it seem that genetic testing could be useful in terms of quantifying disease risk or guiding treatment.
Research has increased our knowledge about the relationship between naturally occurring genetic variation and risk of hypertension. Although some results serve to confirm our understanding of underlying physiology, their value in terms of potentially leading to practical advances in the management of hypertension appears questionable.
Electrostatic analyzers of different designs have been used since the earliest days of the space age, beginning with the very earliest solar-wind measurements made by Mariner 2 en route to Venus in ...1962. The Parker Solar Probe (PSP) mission, NASA's first dedicated mission to study the innermost reaches of the heliosphere, makes its thermal plasma measurements using a suite of instruments called the Solar Wind Electrons, Alphas, and Protons (SWEAP) investigation. SWEAP's electron PSP Analyzer (Solar Probe ANalyzer-Electron (SPAN-E)) instruments are a pair of top-hat electrostatic analyzers on PSP that are capable of measuring the electron distribution function in the solar wind from 2 eV to 30 keV. For the first time, in situ measurements of thermal electrons provided by SPAN-E will help reveal the heating and acceleration mechanisms driving the evolution of the solar wind at the points of acceleration and heating, closer than ever before to the Sun. This paper details the design of the SPAN-E sensors and their operation, data formats, and measurement caveats from PSP's first two close encounters with the Sun.
Introduction: A previous study of 200,000 exome-sequenced UK Biobank participants to test for association of rare coding variants with hypertension implicated two genes at exome-wide significance, ...DNMT3A and FES. A total of 42 genes had an uncorrected p value <0.001. These results were followed up in a larger sample of 470,000 exome-sequenced participants. Methods: Weighted burden analysis of rare coding variants in a new sample of 97,050 cases and 172,263 controls was carried out for these 42 genes. Those showing evidence for association were then analysed in the combined sample of 167,127 cases and 302,691 controls. Results: The association of DNMT3A and FES with hypertension was replicated in the new sample and they and the previously implicated gene NPR1, which codes for a membrane-bound guanylate cyclase, were all exome-wide significant in the combined sample. Also exome-wide significant as risk genes for hypertension were GUCY1A1, ASXL1, and SMAD6, while GUCY1B1 had a nominal p value of <0.0001. GUCY1A1 and GUCY1B1 code for subunits of a soluble guanylate cyclase. For two genes, DBH, which codes for dopamine beta hydroxylase, and INPPL1, rare coding variants predicted to impair gene function were protective against hypertension, again with exome-wide significance. Conclusion: The findings offer new insights into biological risk factors for hypertension which could be the subject of further investigation. In particular, genetic variants predicted to impair the function of either membrane-bound guanylate cyclase, activated by natriuretic peptides, or soluble guanylate cyclase, activated by nitric oxide, increase risk of hypertension. Conversely, variants impairing the function of dopamine beta hydroxylase, responsible for the synthesis of norepinephrine, reduce hypertension risk.
Objectives
Experiences of vicarious racism—hearing about racism directed toward one’s racial group or racist acts committed against other racial group members—and vigilance about racial ...discrimination have been salient during the COVID-19 pandemic. This study examined vicarious racism and vigilance in relation to symptoms of depression and anxiety among Asian and Black Americans.
Methods
We used data from a cross-sectional study of 604 Asian American and 844 Black American adults aged ≥18 in the United States recruited from 5 US cities from May 21 through July 15, 2020. Multivariable linear regression models examined levels of depression and anxiety by self-reported vicarious racism and vigilance.
Results
Controlling for sociodemographic characteristics, among both Asian and Black Americans, greater self-reported vicarious racism was associated with more symptoms of depression (Asian: β = 1.92 95% CI, 0.97-2.87; Black: β = 1.72 95% CI, 0.95-2.49) and anxiety (Asian: β = 2.40 95% CI, 1.48-3.32; Black: β = 1.98 95% CI, 1.17-2.78). Vigilance was also positively related to symptoms of depression (Asian: β = 1.54 95% CI, 0.58-2.50; Black: β = 0.90 95% CI, 0.12-1.67) and anxiety (Asian: β = 1.98 95% CI, 1.05-2.91; Black: β = 1.64 95% CI, 0.82-2.45).
Conclusions
Mental health problems are a pressing concern during the COVID-19 pandemic. Results from our study suggest that heightened racist sentiment, harassment, and violence against Asian and Black Americans contribute to increased risk of depression and anxiety via vicarious racism and vigilance. Public health efforts during this period should address endemic racism as well as COVID-19.
Highly public anti-Black violence in the United States may cause widely experienced distress for Black Americans. This study identifies 49 publicized incidents of racial violence and quantifies ...national interest based on Google searches; incidents include police killings of Black individuals, decisions not to indict or convict the officer involved, and hate crime murders. Weekly time series of population mental health are produced for 2012 through 2017 using two sources: 1) Google Trends as national search volume for psychological distress terms and 2) the Behavioral Risk Factor Surveillance System (BRFSS) as average poor mental health days in the past 30 d among Black respondents (mean weekly sample size of 696). Autoregressive moving average (ARMA) models accounted for autocorrelation, monthly unemployment, season and year effects, 52-wk lags, news-related searches for suicide (for Google Trends), and depression prevalence and percent female (for BRFSS). National search interest varied more than 100-fold between racial violence incidents. Black BRFSS respondents reported 0.26 more poor mental health days during weeks with two or more racial incidents relative to none, and 0.13 more days with each log
increase in national interest. Estimates were robust to sensitivity tests, including controlling for monthly number of Black homicide victims and weekly search interest in riots. As expected, racial incidents did not predict average poor mental health days among White BRFSS respondents. Results with national psychological distress from Google Trends were mixed but generally unsupportive of hypotheses. Reducing anti-Black violence may benefit Black Americans' mental health nationally.
Objective: There is some evidence to suggest that one's ability to delay gratification is associated with a lower body mass index (BMI) and slower overall weight gain. Less is known about the role ...that a broader set of self-regulatory skills, including attention focusing, inhibitory control, and impulsivity, might play in fostering not only a healthy weight but also better overall health and health-related behaviors such as sleep. Method: Participants in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development were followed from birth through age 15 beginning in 1991. Self-regulation was assessed when children were 4.5 years old, whereas health-related outcomes were assessed regularly between toddlerhood and adolescence. Structural equation modeling was used to test direct associations between self-regulation and either physical health or sleep in childhood and adolescence. Results: Findings suggest that there are long-term benefits of self-regulation, indexed by multiple dimensions, for children's health-related outcomes. Children with better self-regulatory skills demonstrated smaller increases in standardized BMI scores and maintained greater mother-reported health across childhood and adolescence. Furthermore, better self-regulation predicted fewer sleep problems and longer sleep duration when children were 8 and 11 but not when they were 15. Conclusions: Early self-regulation, marked by numerous skills, appears to have long-term benefits for children's health-related outcomes. These findings provide some evidence that targeting childhood self-regulatory skills for improvement may help reduce poor health-related outcomes later in life and offer important insight into potential avenues for intervention.
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