A Genetic Study of Cerebral Atherosclerosis Reveals Novel Associations with NTNG1 and CNOT3

Cerebral atherosclerosis is a leading cause of stroke and an important contributor to dementia. Yet little is known about its genetic basis. To examine the association of common single nucleotide polymorphisms with cerebral atherosclerosis severity, we conducted a genomewide association study (GWAS) using data collected as part of two community-based cohort studies in the United States, the Religious Orders Study (ROS) and Rush Memory and Aging Project (MAP). Both studies enroll older individuals and exclude participants with signs of dementia at baseline. From our analysis of 1325 participants of European ancestry who had genotype and neuropathologically assessed cerebral atherosclerosis measures available, we found a novel locus for cerebral atherosclerosis in NTNG1. The locus comprises eight SNPs, including two independent significant SNPs: rs6664221 (β = −0.27, 95% CI = (−0.35, −0.19), p = 1.29 × 10−10) and rs10881463 (β = −0.20, 95% CI = (−0.27, −0.13), p = 3.40 × 10−8). We further found that the SNPs may influence cerebral atherosclerosis by regulating brain protein expression of CNOT3. CNOT3 is a subunit of CCR4−NOT, which has been shown to be a master regulator of mRNA stability and translation and an important complex for cholesterol homeostasis. In summary, we identify a novel genetic locus for cerebral atherosclerosis and a potential mechanism linking this variation to cerebral atherosclerosis progression. These findings offer insights into the genetic effects on cerebral atherosclerosis.

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Alcohol-Related Deaths and Hospitalizations by Race, Gender, and Age in California

The Open Epidemiology Journal ◽

10.2174/1874297101003010003 ◽

2010 ◽

Vol 3 (1) ◽

pp. 3-15 ◽

Cited By ~ 9

Author(s):

Mandy Stahre ◽

Michele Simon

Keyword(s):

Alcohol Use ◽

Race And Ethnicity ◽

Motor Vehicle ◽

The United States ◽

Chronic Illnesses ◽

Older Individuals ◽

Gender And Age ◽

Excessive Alcohol ◽

Race Ethnicity ◽

Using Data

Introduction: Excessive alcohol use is the third leading preventable cause of death in the United States each year and responsible for about 10,000 deaths in California alone. In addition, excessive alcohol use is responsible for many hospitalizations due to injuries and illnesses. Alcohol consumption is known to differ by age, sex, and race/ethnicity and these consumption patterns can lead to differences in alcohol-related outcomes. Methods: Using data from a variety of sources, alcohol-attributable deaths and nonfatal hospitalizations for illnesses and injuries were calculated for California for the year 2006. Results: Excessive alcohol use resulted in over 10,000 deaths and 72,000 nonfatal hospitalizations in California. The majority of consequences (51%) were due to chronic illnesses associated with long-term excessive use of alcohol. Overall, males reported more deaths and nonfatal hospitalizations due to excessive alcohol use than women. Alcohol-attributable deaths and hospitalizations are more likely to occur among individuals aged 50-64 years for illnesses and individuals aged 20-34 years for injuries. Older individuals suffered from more chronic conditions such as alcoholic liver disease, while younger individuals were more likely to suffer from injuries, the most common being motor-vehicle traffic crashes. Significant differences in the rate of deaths and nonfatal hospitalizations by race/ethnicity were more common due to injuries and violence than chronic diseases. Conclusions: This study highlighted key findings of demographic differences in consequences suffered by excessive alcohol use in California. Continued efforts to better evaluate the contribution of alcohol to morbidity and mortality by demographic factors, especially by race and ethnicity, is warranted to prevent and reduce the harm associated with this behavior.

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Migration and the Internet

MIGRATION LETTERS ◽

10.33182/ml.v14i3.347 ◽

2017 ◽

Vol 14 (3) ◽

pp. 331-342 ◽

Cited By ~ 6

Author(s):

Thomas John Cooke ◽

Ian Shuttleworth

Keyword(s):

United States ◽

Information And Communication Technologies ◽

Unobserved Heterogeneity ◽

Panel Study ◽

The United States ◽

Negative Effect ◽

Information And Communication ◽

Using Data ◽

And Migration ◽

Dynamics Models

It is widely presumed that information and communication technologies, or ICTs, enable migration in several ways; primarily by reducing the costs of migration. However, a reconsideration of the relationship between ICTs and migration suggests that ICTs may just as well hinder migration; primarily by reducing the costs of not moving. Using data from the US Panel Study of Income Dynamics, models that control for sources of observed and unobserved heterogeneity indicate a strong negative effect of ICT use on inter-state migration within the United States. These results help to explain the long-term decline in internal migration within the United States.

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EpiPen: An R Package to Investigate Two-Locus Epistatic Models

Twin Research and Human Genetics ◽

10.1017/thg.2014.25 ◽

2014 ◽

Vol 17 (4) ◽

Cited By ~ 2

Author(s):

Raymond K. Walters ◽

Charles Laurin ◽

Gitta H. Lubke

Keyword(s):

Power Analysis ◽

R Package ◽

Simulation Studies ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Epistatic Interactions ◽

Model Interpretation ◽

Genome Wide ◽

Using Data ◽

Power Analyses

Epistasis is a growing area of research in genome-wide studies, but the differences between alternative definitions of epistasis remain a source of confusion for many researchers. One problem is that models for epistasis are presented in a number of formats, some of which have difficult-to-interpret parameters. In addition, the relation between the different models is rarely explained. Existing software for testing epistatic interactions between single-nucleotide polymorphisms (SNPs) does not provide the flexibility to compare the available model parameterizations. For that reason we have developed an R package for investigating epistatic and penetrance models, EpiPen, to aid users who wish to easily compare, interpret, and utilize models for two-locus epistatic interactions. EpiPen facilitates research on SNP-SNP interactions by allowing the R user to easily convert between common parametric forms for two-locus interactions, generate data for simulation studies, and perform power analyses for the selected model with a continuous or dichotomous phenotype. The usefulness of the package for model interpretation and power analysis is illustrated using data on rheumatoid arthritis.

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Challenges in Bridge Health Monitoring: A Review

Sensors ◽

10.3390/s21134336 ◽

2021 ◽

Vol 21 (13) ◽

pp. 4336

Author(s):

Piervincenzo Rizzo ◽

Alireza Enshaeian

Keyword(s):

United States ◽

Health Monitoring ◽

Highway Bridges ◽

The United States ◽

Anomalous Behavior ◽

Existing Structures ◽

Bridge Health Monitoring ◽

Using Data ◽

The Many ◽

Major Factors

Bridge health monitoring is increasingly relevant for the maintenance of existing structures or new structures with innovative concepts that require validation of design predictions. In the United States there are more than 600,000 highway bridges. Nearly half of them (46.4%) are rated as fair while about 1 out of 13 (7.6%) is rated in poor condition. As such, the United States is one of those countries in which bridge health monitoring systems are installed in order to complement conventional periodic nondestructive inspections. This paper reviews the challenges associated with bridge health monitoring related to the detection of specific bridge characteristics that may be indicators of anomalous behavior. The methods used to detect loss of stiffness, time-dependent and temperature-dependent deformations, fatigue, corrosion, and scour are discussed. Owing to the extent of the existing scientific literature, this review focuses on systems installed in U.S. bridges over the last 20 years. These are all major factors that contribute to long-term degradation of bridges. Issues related to wireless sensor drifts are discussed as well. The scope of the paper is to help newcomers, practitioners, and researchers at navigating the many methodologies that have been proposed and developed in order to identify damage using data collected from sensors installed in real structures.

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Assessing the Relationships Between COVID-19 Stay-at-Home Orders and Opioid Overdoses in the State of Pennsylvania

Journal of Drug Issues ◽

10.1177/00220426211006362 ◽

2021 ◽

pp. 002204262110063

Author(s):

Brian King ◽

Ruchi Patel ◽

Andrea Rishworth

Keyword(s):

Age Groups ◽

The United States ◽

Opioid Use Disorder ◽

Opioid Overdose ◽

Policy Recommendations ◽

Opioid Use ◽

Fentanyl Analogs ◽

Measure Change ◽

Using Data ◽

At Home

COVID-19 is compounding opioid use disorder throughout the United States. While recent commentaries provide useful policy recommendations, few studies examine the intersection of COVID-19 policy responses and patterns of opioid overdose. We examine opioid overdoses prior to and following the Pennsylvania stay-at-home order implemented on April 1, 2020. Using data from the Pennsylvania Overdose Information Network, we measure change in monthly incidents of opioid-related overdose pre- versus post-April 1, and the significance of change by gender, age, race, drug class, and naloxone doses administered. Findings demonstrate statistically significant increases in overdose incidents among both men and women, White and Black groups, and several age groups, most notably the 30–39 and 40–49 ranges, following April 1. Significant increases were observed for overdoses involving heroin, fentanyl, fentanyl analogs or other synthetic opioids, pharmaceutical opioids, and carfentanil. The study emphasizes the need for opioid use to be addressed alongside efforts to mitigate and manage COVID-19 infection.

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A Behavioral-Analytic Model for Assessing Stress in Firefighters

Behavior Modification ◽

10.1177/0145445520986137 ◽

2021 ◽

pp. 014544552098613

Author(s):

Bailee B. Schuhmann ◽

Sarah N. Henderson ◽

Ryan A. Black ◽

Vincent B. Van Hasselt ◽

Kristin Klimley Margres ◽

...

Keyword(s):

Stress Reduction ◽

Discriminant Validity ◽

Stress Test ◽

The United States ◽

Fire Service ◽

Analytic Model ◽

Negative Effects ◽

Internal Reliability ◽

Convergent And Discriminant Validity ◽

Using Data

Research has documented a number of acute and chronic stressors unique to the fire service. Due to the rise in mental health concerns in firefighters, there has been increased awareness of the negative effects of unmanaged stress. The present study employed a behavioral-analytic model to construct a brief screening measure of stress for this population: the Firefighter Assessment of Stress Test (FAST). Psychometric properties of the FAST were evaluated using data from active-duty firefighters throughout the United States. Results indicated the FAST has good internal reliability ( α = 0.89), as well as good convergent and discriminant validity. Also, the factor structure of the FAST revealed three significant subscales reflective of stress associated with responding to calls, administrative difficulties, and being overworked. Scoring and interpretation guidelines were established to suggest when further assessment is warranted. The FAST offers a brief and valid method of self-assessment of current stress levels in firefighters. Information obtained from the FAST (i.e., overall stress level and domains) has the potential to facilitate more immediate identification and recognition of stress in firefighters than what has been possible to date. Moreover, heightened awareness of stress and its effects will hopefully culminate in expanded efforts directed toward stress reduction and intervention for firefighters and their families.

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Causal Association between Periodontitis and Parkinson’s Disease: A Bidirectional Mendelian Randomization Study

Genes ◽

10.3390/genes12050772 ◽

2021 ◽

Vol 12 (5) ◽

pp. 772

Author(s):

João Botelho ◽

Vanessa Machado ◽

José João Mendes ◽

Paulo Mascarenhas

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Instrumental Variables ◽

Mendelian Randomization ◽

Association Studies ◽

European Ancestry ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genetic Liability ◽

Bidirectional Association

The latest evidence revealed a possible association between periodontitis and Parkinson’s disease (PD). We explored the causal relationship of this bidirectional association through two-sample Mendelian randomization (MR) in European ancestry populations. To this end, we used openly accessible data of genome-wide association studies (GWAS) on periodontitis and PD. As instrumental variables for periodontitis, seventeen single-nucleotide polymorphisms (SNPs) from a GWAS of periodontitis (1817 periodontitis cases vs. 2215 controls) and eight non-overlapping SNPs of periodontitis from an additional GWAS for validation purposes. Instrumental variables to explore for the reverse causation included forty-five SNPs from a GWAS of PD (20,184 cases and 397,324 controls). Multiple approaches of MR were carried-out. There was no evidence of genetic liability of periodontitis being associated with a higher risk of PD (B = −0.0003, Standard Error [SE] 0.0003, p = 0.26). The eight independent SNPs (B = −0.0000, SE 0.0001, p = 0.99) validated this outcome. We also found no association of genetically primed PD towards periodontitis (B = −0.0001, SE 0.0001, p = 0.19). These MR study findings do not support a bidirectional causal genetic liability between periodontitis and PD. Further GWAS studies are needed to confirm the consistency of these results.

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Role Stress and Sense of Control Predict Using Food to Cope With Stress in Midlife Women

Journal of Aging and Health ◽

10.1177/08982643211011020 ◽

2021 ◽

pp. 089826432110110

Author(s):

Dana R. Riedy ◽

Ashley MacPherson ◽

Natalie D. Dautovich

Keyword(s):

Work Stress ◽

Underlying Mechanism ◽

The United States ◽

Role Stress ◽

Work And Family ◽

Midlife Women ◽

Sense Of Control ◽

Study Results ◽

Using Data ◽

Significant Mediator

Objective: The current study examined the association between role stress and using food to cope with stress in midlife women and examined sense of control as a potential underlying mechanism. Methods: An archival analysis was performed using data from 638 midlife women from the Midlife in the United States II study. Results: Hierarchical linear regression analyses demonstrated that work stress (β = .180, p < .001) and family stress (β = .138, p < .05) significantly predicted using food to cope with stress. Sense of control was a significant mediator between work stress and using food to cope with stress ( b = 0.02, 95% CI [.0014, .0314]). Discussion: Midlife women with higher role stress related to work and family are more likely to use food to cope with stress, and sense of control seems to be the link between work stress and using food to cope.

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PSV-13 Genetic parameters and quantitative trait loci for heat stress related traits in sheep

Journal of Animal Science ◽

10.1093/jas/skaa054.289 ◽

2020 ◽

Vol 98 (Supplement_3) ◽

pp. 163-164

Author(s):

Devin R Jacobs ◽

Claudia E Silvera-Rojas ◽

Jennifer M Bormann ◽

Terry A Gipson ◽

Arthur L Goetsch ◽

...

Keyword(s):

Heat Stress ◽

Quantitative Trait Loci ◽

Rectal Temperature ◽

Quantitative Trait ◽

Fixed Effects ◽

Univariate Analysis ◽

Average Daily Gain ◽

The United States ◽

Nucleotide Polymorphisms ◽

Trait Loci

Abstract Greater selection emphasis has been placed on efficiency than on fitness in livestock populations over the last several decades. Heat stress is a concern in production systems due to the negative effects on production, reproduction, and immunity. The objective of the study was to estimate variance components and identify quantitative trait loci (QTL) for heat stress related traits in sheep. A total of 125 Dorper, Katahdin, and St. Croix ewes originating from four regions of the United States were selected for the experiment. Animals were separated into four trials due to facility limitations. Data were collected for each trial over four consecutive two-week periods in an environmentally controlled facility with targeted heat load index (HLI) for daytime/nighttime of 70/70, 85/77, 90/77, and 95/81. Body weight was collected three times per week and rectal temperature was collected weekly. Black globe temperature and humidity were measured every 15 minutes. Animals were genotyped using the Illumina OvineSNP50 BeadChip. After quality control, 49,396 effective single nucleotide polymorphisms were included in the univariate analysis performed with the BLUPF90 suite of programs. Fixed effects in the models included region of origin, breed, trial, and age as a covariate. Traits analyzed included rectal temperature at 95 HLI (RT95), feed intake at 95 HLI (FI95), and average daily gain for the period for HLI between 90 and 95 (ADG). Heritabilities for RT95, FI95, and ADG were 0.35, 0.10, and 0.10, respectively. Largest effect QTL were identified on chromosomes 23, 9, and 6 for RT95, chromosomes 9, 2, and 20 for FI95, and chromosomes 6, 1, and 5 for ADG. Many of the regions identified have also been associated with weight and carcass traits in other studies, but few had obvious connections to the heat stress related response. In conclusion, results suggest selection could improve heat tolerance in sheep.

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Appetite disinhibition rather than hunger explains genetic effects on adult BMI trajectory

International Journal of Obesity ◽

10.1038/s41366-020-00735-9 ◽

2021 ◽

Author(s):

Eric J. Brunner ◽

Koutatsu Maruyama ◽

Martin Shipley ◽

Noriko Cable ◽

Hiroyasu Iso ◽

...

Keyword(s):

Weight Gain ◽

Genetic Susceptibility ◽

Eating Behaviors ◽

Mixed Model ◽

Adult Life ◽

Cohort Effect ◽

The Body ◽

European Ancestry ◽

Nucleotide Polymorphisms ◽

Bmi Trajectories

Abstract Background/objectives The mediating role of eating behaviors in genetic susceptibility to weight gain during mid-adult life is not fully understood. This longitudinal study aims to help us understand contributions of genetic susceptibility and appetite to weight gain. Subjects/methods We followed the body-mass index (BMI) trajectories of 2464 adults from 45 to 65 years of age by measuring weight and height on four occasions at 5-year intervals. Genetic risk of obesity (gene risk score: GRS) was ascertained, comprising 92 BMI-associated single-nucleotide polymorphisms and split at a median (=high and low risk). At the baseline, the Eating Inventory was used to assess appetite-related traits of ‘disinhibition’, indicative of opportunistic eating or overeating and ‘hunger’ which is susceptibility to/ability to cope with the sensation of hunger. Roles of the GRS and two appetite-related scores for BMI trajectories were examined using a mixed model adjusted for the cohort effect and sex. Results Disinhibition was associated with higher BMI (β = 2.96; 95% CI: 2.66–3.25 kg/m2), and accounted for 34% of the genetically-linked BMI difference at age 45. Hunger was also associated with higher BMI (β = 1.20; 0.82–1.59 kg/m2) during mid-life and slightly steeper weight gain, but did not attenuate the effect of disinhibition. Conclusions Appetite disinhibition is most likely to be a defining characteristic of genetic susceptibility to obesity. High levels of appetite disinhibition, rather than hunger, may underlie genetic vulnerability to obesogenic environments in two-thirds of the population of European ancestry.

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