scholarly journals Evaluating the effects of cardiometabolic exposures on circulating proteins which may contribute to SARS-CoV-2 severity

2020 ◽  
Author(s):  
Tom G Richardson ◽  
Si Fang ◽  
Ruth E Mitchell ◽  
Michael V Holmes ◽  
George Davey Smith
Keyword(s):  
Risk Factors ◽  
Multiple Testing ◽  
Interleukin 1 ◽  
The Body ◽  
Sensitivity Analyses ◽  
Future Research ◽  
Current Case ◽  
Regulatory Variants ◽  
Global Pandemic ◽  
Antibody Class

Background: Developing insight into the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to overcome the global pandemic caused by coronavirus disease 2019 (covid-19). In this study, we have applied Mendelian randomization (MR) to systematically evaluate the effect of 10 cardiometabolic risk factors and genetic liability to lifetime smoking on 97 circulating host proteins postulated to either interact or contribute to the maladaptive host response of SARS-CoV-2. Methods: We applied the inverse variance weighted (IVW) approach and several robust MR methods in a two-sample setting to systemically estimate the genetically predicted effect of each risk factor in turn on levels of each circulating protein. Multivariable MR was conducted to simultaneously evaluate the effects of multiple risk factors on the same protein. We also applied MR using cis-regulatory variants at the genomic location responsible for encoding these proteins to estimate whether their circulating levels may influence SARS-CoV-2 severity. Findings: In total, we identified evidence supporting 105 effects between risk factors and circulating proteins which were robust to multiple testing corrections and sensitivity analyses. For example, body mass index provided evidence of an effect on 23 circulating proteins with a variety of functions, such as inflammatory markers c-reactive protein (IVW Beta=0.34 per standard deviation change, 95% CI=0.26 to 0.41, P=2.19x10-16) and interleukin-1 receptor antagonist (IVW Beta=0.23, 95% CI=0.17 to 0.30, P=9.04x10-12). Further analyses using multivariable MR provided evidence that the effect of BMI on lowering immunoglobulin G, an antibody class involved in protecting the body from infection, is substantially mediated by raised triglycerides levels (IVW Beta=-0.18, 95% CI=-0.25 to -0.12, P=2.32x10-08, proportion mediated=44.1%). The strongest evidence that any of the circulating proteins highlighted by our initial analysis influence SARS-CoV-2 severity was identified for soluble glycoprotein 130 (odds ratio=1.81, 95% CI=1.25 to 2.62, P=0.002), a signal transductor for interleukin-6 type cytokines which are involved in the bodys inflammatory response. However, based on current case samples for severe SARS-CoV-2 we were unable to replicate findings in independent samples. Interpretation: Our findings highlight several key proteins which are influenced by established exposures for disease. Future research to determine whether these circulating proteins mediate environmental effects onto risk of SARS-CoV-2 are warranted to help elucidate therapeutic strategies for covid-19 disease severity.

scholarly journals Association of genetically predicted blood sucrose with coronary heart disease and its risk factors in Mendelian randomization

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ting Zhang ◽  
Shiu Lun Au Yeung ◽  
C. Mary Schooling
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Dental Caries ◽  
Multiple Testing ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Sensitivity Analyses ◽  
Genome Wide Association Studies ◽  
Standard Deviation Increase

AbstractWe assessed the associations of genetically instrumented blood sucrose with risk of coronary heart disease (CHD) and its risk factors (i.e., type 2 diabetes, adiposity, blood pressure, lipids, and glycaemic traits), using two-sample Mendelian randomization. We used blood fructose as a validation exposure. Dental caries was a positive control outcome. We selected genetic variants strongly (P < 5 × 10–6) associated with blood sucrose or fructose as instrumental variables and applied them to summary statistics from the largest available genome-wide association studies of the outcomes. Inverse-variance weighting was used as main analysis. Sensitivity analyses included weighted median, MR-Egger and MR-PRESSO. Genetically higher blood sucrose was positively associated with the control outcome, dental caries (odds ratio [OR] 1.04 per log10 transformed effect size [median-normalized standard deviation] increase, 95% confidence interval [CI] 1.002–1.08, P = 0.04), but this association did not withstand allowing for multiple testing. The estimate for blood fructose was in the same direction. Genetically instrumented blood sucrose was not clearly associated with CHD (OR 1.01, 95% CI 0.997–1.02, P = 0.14), nor with its risk factors. Findings were similar for blood fructose. Our study found some evidence of the expected detrimental effect of sucrose on dental caries but no effect on CHD. Given a small effect on CHD cannot be excluded, further investigation with stronger genetic predictors is required.

scholarly journals Can Obesity Prevalence Explain COVID-19 Indicators (Cases, Mortality and Recovery)? A Comparative Study in OECD Countries

2020 ◽  
Author(s):  
Yuval Arbel ◽  
Chaim Fialkoff ◽  
Amichai Kerner ◽  
Miryam Kerner
Keyword(s):  
Risk Factors ◽  
Empirical Studies ◽  
Linear Increase ◽  
Future Research ◽  
Obesity Prevalence ◽  
Ethical Guidelines ◽  
Global Pandemic ◽  
Prevalence Of Obesity ◽  
Competing Models ◽  
Complex Relationships

Abstract Coronavirus disease 2019 (COVID-19) is a declared global pandemic with multiple risk factors. Obesity is considered by several researchers as one of the serious risk factors for coronavirus complications based on recent empirical studies. Yet, other scholars argue in favor of the existence of an obesity survival paradox, and criticize the former group of studies on the grounds that they lack controls for race, socioeconomic status, or quality of care. The objective of the current study is to analyze the potential relationships between different corona indicators and obesity on a state-wide level, based on an OECD report. In an attempt to test the counter-intuitive possibility of an obesity survival paradox, the proposed empirical model relaxes the assumption of monotonic change by applying the quadratic design and testing which one of the two competing models (i.e., quadratic or linear) better fits the data. Findings suggest more complex relationships between corona indices and obesity rates than previously thought. Consequently, ethical guidelines referring to priority in intubation and intensive care treatments should account for these complex relationships between obesity and corona. Indeed, there is a linear increase of mortality rate from corona with elevated prevalence of obesity. Yet, other indicators, such as the number of infected per 100,000 persons, rates of severe corona cases, rates of recovered corona patients and corona as the cause of death exhibit quadratic, rather than linear, patterns. The reasons for these non-linear patterns might be explained by several conditions such as increased metabolic reserves, more aggressive treatment, other non-corona complications for obese persons and unidentified factors that should be examined in future research.

scholarly journals The Diets of Companion Cats in Aotearoa New Zealand: Identification of Obesity Risk Factors

Animals ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2881
Author(s):  
Rachel Forrest ◽  
Leena Awawdeh ◽  
Fiona Esam ◽  
Maria Pearson ◽  
Natalie Waran
Keyword(s):  
Risk Factors ◽  
New Zealand ◽  
Body Condition ◽  
Online Survey ◽  
Caloric Intake ◽  
The Body ◽  
Future Research ◽  
Healthy Weight ◽  
Veterinary Clinic ◽  
Related Risk

One in four New Zealand cats are overweight or obese, conditions associated with poor health outcomes. As part of an online survey that was conducted from January 2019 to March 2019, NZ residents aged ≥18 years were asked demographic questions along with questions related to the body condition, breed and diet of their cat/s. From the responses, possible owner-related risk factors for developing obesity were identified. Of the respondents, 65.5% (n = 1537) owned cat/s; the owners being more likely to be female, live rurally, or live with children. Most of the respondents fed their cat/s biscuits from the supermarket (63%) and wet food (57%). Almost half (45%) fed their cat/s specialised food from a pet shop or veterinary clinic and gave them treats, with 31% of respondents feeding their cat/s raw meat. Feeding cats a variety of food types may make it difficult to estimate the appropriate amount of each needed to avoid excess caloric intake. In addition, approximately 30% of the respondents did not agree with the correct body condition statement, revealing a need for owner education. These findings highlight important areas of cat nutrition requiring future research to better inform the development of healthy weight interventions for NZ cats.

scholarly journals Inflammatory Regulation of CNS Barriers After Traumatic Brain Injury: A Tale Directed by Interleukin-1

2021 ◽  
Vol 12 ◽  
Author(s):  
Colleen N. Bodnar ◽  
James B. Watson ◽  
Emma K. Higgins ◽  
Ning Quan ◽  
Adam D. Bachstetter
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Immune Cells ◽  
Interleukin 1 ◽  
Brain Lesion ◽  
The Body ◽  
Future Research ◽  
Secondary Injury ◽  
Inflammatory Regulation ◽  
The Brain

Several barriers separate the central nervous system (CNS) from the rest of the body. These barriers are essential for regulating the movement of fluid, ions, molecules, and immune cells into and out of the brain parenchyma. Each CNS barrier is unique and highly dynamic. Endothelial cells, epithelial cells, pericytes, astrocytes, and other cellular constituents each have intricate functions that are essential to sustain the brain’s health. Along with damaging neurons, a traumatic brain injury (TBI) also directly insults the CNS barrier-forming cells. Disruption to the barriers first occurs by physical damage to the cells, called the primary injury. Subsequently, during the secondary injury cascade, a further array of molecular and biochemical changes occurs at the barriers. These changes are focused on rebuilding and remodeling, as well as movement of immune cells and waste into and out of the brain. Secondary injury cascades further damage the CNS barriers. Inflammation is central to healthy remodeling of CNS barriers. However, inflammation, as a secondary pathology, also plays a role in the chronic disruption of the barriers’ functions after TBI. The goal of this paper is to review the different barriers of the brain, including (1) the blood-brain barrier, (2) the blood-cerebrospinal fluid barrier, (3) the meningeal barrier, (4) the blood-retina barrier, and (5) the brain-lesion border. We then detail the changes at these barriers due to both primary and secondary injury following TBI and indicate areas open for future research and discoveries. Finally, we describe the unique function of the pro-inflammatory cytokine interleukin-1 as a central actor in the inflammatory regulation of CNS barrier function and dysfunction after a TBI.

Attachment Organization in Suicide Prevention Research

Crisis ◽  
2014 ◽  
Vol 35 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Amanda Venta ◽  
Carla Sharp
Keyword(s):  
Risk Factors ◽  
Suicidal Ideation ◽  
Suicide Attempt ◽  
Interpersonal Relationships ◽  
Suicide Ideation ◽  
Suicide Attempts ◽  
Critical Role ◽  
Self Report ◽  
Future Research ◽  
Self Harm

Background: Identifying risk factors for suicide-related thoughts and behaviors (SRTB) is essential among adolescents in whom SRTB remain a leading cause of death. Although many risk factors have already been identified, influential theories now suggest that the domain of interpersonal relationships may play a critical role in the emergence of SRTB. Because attachment has long been seen as the foundation of interpersonal functioning, we suggest that attachment insecurity warrants attention as a risk factor for SRTB. Aims: This study sought to explore relations between attachment organization and suicidal ideation, suicide attempts, and self-harm in an inpatient adolescent sample, controlling for demographic and psychopathological covariates. Method: We recruited 194 adolescents from an inpatient unit and assigned them to one of four attachment groups (secure, preoccupied, dismissing, or disorganized attachment). Interview and self-report measures were used to create four variables reflecting the presence or absence of suicidal ideation in the last year, single lifetime suicide attempt, multiple lifetime suicide attempts, and lifetime self-harm. Results: Chi-square and regression analyses did not reveal significant relations between attachment organization and SRTB, although findings did confirm previously established relations between psychopathology and SRTB, such that internalizing disorder was associated with increased self-harm, suicide ideation, and suicide attempt and externalizing disorder was associated with increased self-harm. Conclusion: The severity of this sample and methodological differences from previous studies may explain the nonsignificant findings. Nonsignificant findings may indicate that the relation between attachment organization and SRTB is moderated by other factors that should be explored in future research.

Political psychology in the digital (mis)information age: A model of news belief and sharing

2020 ◽  
Author(s):  
Jay Joseph Van Bavel ◽  
Elizabeth Ann Harris ◽  
Philip Pärnamets ◽  
Steve Rathje ◽  
Kimberly Doell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cognitive Psychology ◽  
Information Age ◽  
Policy Research ◽  
Integrative Model ◽  
Future Research ◽  
Fake News ◽  
Policy Makers ◽  
Conspiracy Theories ◽  
The Social

The spread of misinformation, including “fake news,” propaganda, and conspiracy theories, represents a serious threat to society, as it has the potential to alter beliefs, behavior, and policy. Research is beginning to disentangle how and why misinformation is spread and identify processes that contribute to this social problem. We propose an integrative model to understand the social, political, and cognitive psychology risk factors that underlie the spread of misinformation and highlight strategies that might be effective in mitigating this problem. However, the spread of misinformation is a rapidly growing and evolving problem; thus scholars need to identify and test novel solutions, and work with policy makers to evaluate and deploy these solutions. Hence, we provide a roadmap for future research to identify where scholars should invest their energy in order to have the greatest overall impact.

Non-Traditional Cardiovascular Risk Markers in the Era of Established Major Risk Factors and Multiple Guidelines

2019 ◽  
Vol 17 (3) ◽  
pp. 270-277 ◽  
Author(s):  
Thomas F. Whayne
Keyword(s):  
Risk Factors ◽  
Interleukin 1 ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
High Sensitivity ◽  
Arterial Disease ◽  
Good Evidence ◽  
Ldl Particles ◽  
Cv Disease ◽  
Peripheral Arterial

The non-traditional cardiovascular (CV) risk factors that appear to be of most clinical interest include: apolipoprotein A (ApoA), apolipoprotein B (ApoB), high-sensitivity C-Reactive protein (hsCRP), homocysteine, interleukin 1 (IL1), lipoprotein (a) [Lp(a)], the density of low-density lipoprotein (LDL) particles, the LDL particle number, tissue/tumor necrosis factor-α (TNF-α) and uric acid. These non-traditional risk factors may be of value in adding further confirmation and attention to suspected significant CV risk. They can also provide a better understanding of current concepts of atherogenesis (e.g. various potential mechanisms associated with inflammation) as an etiology and in guiding current plus future therapies. In the mid-20th century, atherosclerosis and CV disease were considered mechanistic occurrences with essentially no attention to possible metabolic and molecular etiologies. Therefore, the only treatments then centered around mainly surgical procedures to try to improve blood flow, first with peripheral arterial disease (PAD) and later coronary artery disease (CAD). Now, failure to treat CV risk factors, especially where there is good evidence-based medicine, as in the case of statins for high CV risk patients, is considered medical negligence. Nevertheless, many problems remain to be solved regarding atherosclerosis prevention and treatment.

Dysfunctional Behavior in Organizations: Insights from the Management Control Literature

2017 ◽  
Vol 37 (4) ◽  
pp. 117-141 ◽  
Author(s):  
Krista Fiolleau ◽  
Theresa Libby ◽  
Linda Thorne
Keyword(s):  
Risk Factors ◽  
Internal Control ◽  
Management Control ◽  
Future Research ◽  
Fraud Triangle ◽  
Audit Risk ◽  
Research Opportunities ◽  
Dysfunctional Behavior ◽  
Research Questions ◽  
Published Research

SUMMARY As the scope of the audit continues to broaden (Cohen, Krishnamoorthy, and Wright 2017), research questions in management control and internal control are beginning to overlap. Even so, there is little overlap between these fields in terms of published research to date. The purpose of this paper is to take a step in bridging the gap between the management control and the internal control literatures. We survey relevant findings from the extant management control literature published between 2003 and 2016 on dysfunctional behavior and the ways in which it might be mitigated. We then use the fraud triangle as an organizing framework to consider how the management control literature might help to address audit risk factors identified in SAS 99/AU SEC 316 (AICPA 2002). The outcome of our analysis is meant to identify and classify the extant management control literature of relevance to research on internal control in a manner that researchers new to the management control literature will find accessible. We conclude with a set of future research opportunities that can help to broaden the scope of current research in internal control.

scholarly journals Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett’s oesophagus and provides insights into clinical heterogeneity in reflux diagnosis

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323906
Author(s):  
Jue-Sheng Ong ◽  
Jiyuan An ◽  
Xikun Han ◽  
Matthew H Law ◽  
Priyanka Nandakumar ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Testing ◽  
Association Studies ◽  
Barrett’S Oesophagus ◽  
Oesophageal Reflux ◽  
Oesophageal Adenocarcinoma ◽  
Specific Gene ◽  
Genome Wide Association Studies ◽  
Disease Heterogeneity ◽  
Barrett's Oesophagus

ObjectiveGastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett’s oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications.DesignWe applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA).ResultsWe identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA.ConclusionOur multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.

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