Associations Between Daily-Use Products and Urinary Biomarkers of Endocrine-Disrupting Chemicals in Adults of Reproductive Age.

Background: Daily-use products, including personal care products, household products, and dietary supplements, often contain ingredients that raise concerns regarding harmful chemical exposure. Endocrine-disrupting chemicals (EDCs) found in daily-use products are associated with numerous adverse health effects.

Methods: This pilot study explores the relationship between concentrations of EDCs in urine samples and products used 24 h prior to sample collection, and ingredients of concern in those products, in 140 adults of reproductive age in Northern Nevada.

A study of impulsivity and adverse childhood experiences in a population health setting.

As complex mental health traits and life histories are often poorly captured in hospital systems, the utility of using the Barratt Impulsivity Scale (BIS) and Adverse Childhood Experiences (ACEs) for assessing adult disease risks is unknown. Here, we use participants from the Healthy Nevada Project (HNP) to determine if two standard self-assessments could predict the incidence and onset of disease. We conducted a retrospective cohort study involving adult participants who completed the Behavioral and Mental Health Self-Assessment (HDSA) between September 2018 and March 2024.

Combining rare and common genetic variants improves population risk stratification for breast cancer.

Purpose: This study aimed to evaluate the performance of different genetic screening approaches to identify women at high risk of breast cancer in the general population.

Methods: We retrospectively studied 25,591 women with available electronic health records and genetic data, participants in the Healthy Nevada Project.

Results: Family history of breast cancer was ascertained on or after the record of breast cancer for 78% of women with both, indicating that this risk assessment method is not being properly utilized for early screening.

Reducing Exposures to Endocrine Disruptors (REED) study, a personalized at-home intervention program to reduce exposure to endocrine disrupting chemicals among a child-bearing age cohort: study protocol for a randomized controlled trial.

Background: Exposures to endocrine disrupting chemicals (EDCs) have been linked to chronic diseases including breast cancer, metabolic syndrome, diabetes, and infertility. Exposure during pregnancy may have a lifelong impact on the fetus. Services are needed to allow individuals to learn about their personal EDC exposures and how to reduce them.

Underestimated risk of secondary complications in pathogenic and glucose-elevating GCK variant carriers with type 2 diabetes.

Background: Natural HbA1c levels in GCK Maturity-onset diabetes of the young (GCK-MODY) patients often sit above the diagnostic threshold for type 2 diabetes (T2D). Treatments to lower HbA1c levels show reduced effectiveness in these individuals, yet in case studies to date, GCK-MODY patients often evade secondary T2D complications. Given these deviations, genetic screening of GCK may be clinically useful, but population studies are needed to more broadly understand T2D-related complications in GCK variant carriers.

Screening Familial Risk for Hereditary Breast and Ovarian Cancer.

Importance: Most patients with pathogenic or likely pathogenic (P/LP) variants for breast cancer have not undergone genetic testing.

Objective: To identify patients meeting family history criteria for genetic testing in the electronic health record (EHR).

Design, Setting, And Participants: This study included both cross-sectional (observation date, February 1, 2024) and retrospective cohort (observation period, January 1, 2018, to February 1, 2024) analyses.

A Personalized Intervention to Increase Environmental Health Literacy and Readiness to Change in a Northern Nevada Population: Effects of Environmental Chemical Exposure Report-Back.

Background: Interventions are needed to help people reduce exposure to harmful chemicals from everyday products and lifestyle habits. Report-back of individual exposures is a potential pathway to increasing environmental health literacy (EHL) and readiness to reduce exposures.

Objectives: Our objective was to determine if report-back of endocrine-disrupting chemicals (EDCs) can reduce EDC exposure, increase EHL, and increase readiness to change (i.

Germline variants predispose to mesothelioma by impairing DNA repair and calcium signaling.

We report that ~1.8% of all mesothelioma patients and 4.9% of those younger than 55, carry rare germline variants of the BRCA1 associated RING domain 1 ( gene that were predicted to be damaging by computational analyses.

Lack of association between classical HLA genes and asymptomatic SARS-CoV-2 infection.

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs.

A power-based sliding window approach to evaluate the clinical impact of rare genetic variants in the nucleotide sequence or the spatial position of the folded protein.

Systematic determination of novel variant pathogenicity remains a major challenge, even when there is an established association between a gene and phenotype. Here we present Power Window (PW), a sliding window technique that identifies the impactful regions of a gene using population-scale clinico-genomic datasets. By sizing analysis windows on the number of variant carriers, rather than the number of variants or nucleotides, statistical power is held constant, enabling the localization of clinical phenotypes and removal of unassociated gene regions.

SARS-CoV-2 Antiviral Prescribing Gaps Among Nonhospitalized High-Risk Adults.

Within a multistate clinical cohort, SARS-CoV-2 antiviral prescribing patterns were evaluated from April 2022-June 2023 among nonhospitalized patients with SARS-CoV-2 with risk factors for severe COVID-19. Among 3247 adults, only 31.9% were prescribed an antiviral agent (87.

Lack of association between HLA and asymptomatic SARS-CoV-2 infection.

Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B*15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B*15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the US (191 asymptomatic vs.

The Potential of Genetics in Identifying Women at Lower Risk of Breast Cancer.

Importance: Genetic information is not being used to identify women at lower risk of breast cancer or other diseases in clinical practice. With the new US Preventive Services Task Force guidelines lowering the age for mammogram screening for all, there is a potential benefit in identifying women at lower risk of disease who may defer the start of mammographic screening. This genetic risk-based approach would help mitigate overscreening, associated costs, and anxiety.

Clinical case study meets population cohort: identification of a BRCA1 pathogenic founder variant in Orcadians.

We multiply ascertained the BRCA1 pathogenic missense variant c.5207T > C; p.Val1736Ala (V1736A) in clinical investigation of breast and ovarian cancer families from Orkney in the Northern Isles of Scotland, UK.

Cardiomyopathy prevalence exceeds 30% in individuals with TTN variants and early atrial fibrillation.

Purpose: TTN truncating variants (TTNtvs) represent the largest known genetic cause of dilated cardiomyopathies (DCMs), however their penetrance for DCM in general populations is low. More broadly, patients with cardiomyopathies (CMs) often exhibit other cardiac conditions, such as atrial fibrillation (Afib), which has also been linked to TTNtvs. This retrospective analysis aims to characterize the relationship between different cardiac conditions in those with TTNtvs and identify individuals with the highest risk of DCM.

Using phenome-wide association studies and the SF-12 quality of life metric to identify profound consequences of adverse childhood experiences on adult mental and physical health in a Northern Nevadan population.

In this research, we examine and identify the implications of Adverse Childhood Experiences (ACEs) on a range of health outcomes, with particular focus on a number of mental health disorders. Many previous studies observed that traumatic childhood events are linked to long-term adult diseases using the standard Adverse Childhood Experience Questionnaire. The study cohort was derived from the Healthy Nevada Project, a volunteer-based population health study in which each adult participant is invited to take a retrospective questionnaire that includes the Adverse Childhood Experience Questionnaire, the 12-item Short Form Survey measuring quality of life, and self-reported incidence of nine mental disorders.

Naturally occurring metals in unregulated domestic wells in Nevada, USA.

The dominant source of drinking water in rural Nevada, United States, is privately-owned domestic wells. Because the water from these wells is unregulated with respect to government guidelines, it is the owner's responsibility to test their groundwater for heavy metals and other contaminants. Arsenic, lead, cadmium, and uranium have been previously measured at concentrations above Environmental Protection Agency (EPA) guidelines in Nevada groundwater.

Incomplete Penetrance of Population-Based Genetic Screening Results in Electronic Health Record.

The clinical value of population-based genetic screening projects depends on the actions taken on the findings. The Healthy Nevada Project (HNP) is an all-comer genetic screening and research project based in northern Nevada. HNP participants with CDC Tier 1 findings of hereditary breast and ovarian cancer syndrome (HBOC), Lynch syndrome (LS), or familial hypercholesterolemia (FH) are notified and provided with genetic counseling.

The Impact of ACEs on BMI: An Investigation of the Genotype-Environment Effects of BMI.

Adverse Childhood Experiences are stressful and traumatic events occurring before the age of eighteen shown to cause mental and physical health problems, including increased risk of obesity. Obesity remains an ongoing national challenge with no predicted solution. We examine a subset of the Healthy Nevada Project, focusing on a multi-ethnic cohort of 15,886 sequenced participants with recalled adverse childhood events, to study how ACEs and their genotype-environment interactions affect BMI.

HLA-A∗03:01 is associated with increased risk of fever, chills, and stronger side effects from Pfizer-BioNTech COVID-19 vaccination.

COVID-19 vaccines are safe and highly effective, but some individuals experience unpleasant reactions to vaccination. As the majority of adults in the United States have received a COVID-19 vaccine this year, there is an unprecedented opportunity to study the genetics of reactions to vaccination via surveys of individuals who are already part of genetic research studies. Here, we have queried 17,440 participants in the Helix DNA Discovery Project and Healthy Nevada Project about their reactions to COVID-19 vaccination.

Positive predictive value highlights four novel candidates for actionable genetic screening from analysis of 220,000 clinicogenomic records.

Purpose: To identify conditions that are candidates for population genetic screening based on population prevalence, penetrance of rare variants, and actionability.

Methods: We analyzed exome and medical record data from >220,000 participants across two large population health cohorts with different demographics. We performed a gene-based collapsing analysis of rare variants to identify genes significantly associated with disease status.

SARS-CoV-2 test positivity rate in Reno, Nevada: association with PM2.5 during the 2020 wildfire smoke events in the western United States.

Background: Air pollution has been linked to increased susceptibility to SARS-CoV-2. Thus, it has been suggested that wildfire smoke events may exacerbate the COVID-19 pandemic.

Objectives: Our goal was to examine whether wildfire smoke from the 2020 wildfires in the western United States was associated with an increased rate of SARS-CoV-2 infections in Reno, Nevada.

Comprehensive Allele Genotyping in Critical Pharmacogenes Reduces Residual Clinical Risk in Diverse Populations.

Genomic-guided pharmaceutical prescribing is increasingly recognized as an important clinical application of genetics. Accurate genotyping of pharmacogenomic (PGx) genes can be difficult, owing to their complex genetic architecture involving combinations of single-nucleotide polymorphisms and structural variation. Here, we introduce the Helix PGx database, an open-source star allele, genotype, and resulting metabolic phenotype frequency database for CYP2C9, CYP2C19, CYP2D6, and CYP4F2, based on short-read sequencing of >86,000 unrelated individuals enrolled in the Helix DNA Discovery Project.