Decomposed interaction testing improves detection of genetic modifiers of the relationship of dietary omega-3 fatty acid intake and its plasma biomarkers with hsCRP in the UK Biobank.

Discovery and translation of gene-environment interactions (GxEs) influencing clinical outcomes is limited by low statistical power and poor mechanistic understanding. Molecular omics data may help address these limitations, but their incorporation into GxE testing requires principled analytic approaches. We focused on genetic modification of the established mechanistic link between dietary long-chain omega-3 fatty acid (dN3FA) intake, plasma N3FA (pN3FA), and chronic inflammation as measured by high sensitivity CRP (hsCRP).

Multi-trait and multi-ancestry genetic analysis of comorbid lung diseases and traits improves genetic discovery and polygenic risk prediction.

While respiratory diseases such as COPD and asthma share many risk factors, most studies investigate them in insolation and in predominantly European ancestry populations. Here, we conducted the most powerful multi-trait and -ancestry genetic analysis of respiratory diseases and auxiliary traits to date. Our approach improves the power of genetic discovery across traits and ancestries, identifying 44 novel loci associated with lung function in individuals of East Asian ancestry.

Body dissatisfaction widens the racial disparities of Benzophenone-3, a chemical biomarker of personal care and consumer product usage.

Background: Body dissatisfaction can drive individuals to use personal care products, exposing themselves to Benzophenone-3 (BP3). Yet, no study has examined the link between body dissatisfaction and elevated chemical exposures.

Objectives: Our study examines how body dissatisfaction impacts the racial differences in BP3 exposures.

Dissipation kinetics and risk assessment of residues of combination product of two fungicides, fluxapyroxad, and pyraclostrobin in cumin.

Supervised field trial studies were conducted to understand dissipation kinetics and harvest time residues of a combination product of fluxapyroxad and pyraclostrobin in cumin plant/leaves and seeds at different locations in India. The results showed initial accumulation of fluxapyroxad at the levels of 15.4 and 20.

Projected Changes in Statin and Antihypertensive Therapy Eligibility With the AHA PREVENT Cardiovascular Risk Equations.

Importance: Since 2013, the American College of Cardiology (ACC) and American Heart Association (AHA) have recommended the pooled cohort equations (PCEs) for estimating the 10-year risk of atherosclerotic cardiovascular disease (ASCVD). An AHA scientific advisory group recently developed the Predicting Risk of cardiovascular disease EVENTs (PREVENT) equations, which incorporated kidney measures, removed race as an input, and improved calibration in contemporary populations. PREVENT is known to produce ASCVD risk predictions that are lower than those produced by the PCEs, but the potential clinical implications have not been quantified.

Exposome-wide association study of cognition among older adults in the National Health and Nutrition Examination Survey.

Cognitive impairment among older adults is a growing public health challenge and environmental chemicals may be modifiable risk factors. A wide array of chemicals has not yet been tested for association with cognition in an environment-wide association framework. In the US National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2011-2014 cross-sectional cycles, cognition was assessed using the Digit Symbol Substitution Test (DSST, scores 0-117) among participants aged 60 years and older.

PYPE: A pipeline for phenome-wide association and Mendelian randomization in investigator-driven biobank scale analysis.

Phenome-wide association studies (PheWASs) serve as a way of documenting the relationship between genotypes and multiple phenotypes, helping to uncover unexplored genotype-phenotype associations (known as pleiotropy). Secondly, Mendelian randomization (MR) can be harnessed to make causal statements about a pair of phenotypes by comparing their genetic architecture. Thus, approaches that automate both PheWASs and MR can enhance biobank-scale analyses, circumventing the need for multiple tools by providing a comprehensive, end-to-end tool to drive scientific discovery.

Epidemic outcomes following government responses to COVID-19: Insights from nearly 100,000 models.

Government responses to COVID-19 are among the most globally impactful events of the 21st century. The extent to which responses-such as school closures-were associated with changes in COVID-19 outcomes remains unsettled. Multiverse analyses offer a systematic approach to testing a large range of models.

Specification curve analysis to identify heterogeneity in risk factors for dementia: findings from the UK Biobank.

Background: In 2020, the Lancet Commission identified 12 risk factors as priorities for prevention of dementia, and other studies identified APOE e4/e4 genotype and family history of Alzheimer's disease strongly associated with dementia outcomes; however, it is unclear how robust these relationships are across dementia subtypes and analytic scenarios. Specification curve analysis (SCA) is a new tool to probe how plausible analytical scenarios influence outcomes.

Methods: We evaluated the heterogeneity of odds ratios for 12 risk factors reported from the Lancet 2020 report and two additional strong associated non-modifiable factors (APOE e4/e4 genotype and family history of Alzheimer's disease) with dementia outcomes across 450,707 UK Biobank participants using SCA with 5357 specifications across dementia subtypes (outcomes) and analytic models (e.

Implications of Race Adjustment in Lung-Function Equations.

Background: Adjustment for race is discouraged in lung-function testing, but the implications of adopting race-neutral equations have not been comprehensively quantified.

Methods: We obtained longitudinal data from 369,077 participants in the National Health and Nutrition Examination Survey, U.K.

Environmental chemical-wide associations with immune biomarkers in US adults: A cross-sectional analysis.

Environmental chemical exposures influence immune system functions, and humans are exposed to a wide range of chemicals, termed the chemical "exposome". A comprehensive, discovery analysis of the associations of multiple chemical families with immune biomarkers is needed. In this study, we tested the associations between environmental chemical concentrations and immune biomarkers.

Heterogeneity in elevated glucose and A1C as predictors of the prediabetes to diabetes transition: Framingham Heart Study, Multi-Ethnic Study on Atherosclerosis, Jackson Heart Study, and Atherosclerosis Risk In Communities.

Introduction: There are a number of glycemic definitions for prediabetes; however, the heterogeneity in diabetes transition rates from prediabetes across different glycemic definitions in major US cohorts has been unexplored. We estimate the variability in risk and relative risk of adiposity based on diagnostic criteria like fasting glucose and hemoglobin A1C% (HA1C%).

Research Design And Methods: We estimated transition rate from prediabetes, as defined by fasting glucose between 100-125 and/or 110-125 mg/dL, and HA1C% between 5.

Grilling the data: application of specification curve analysis to red meat and all-cause mortality.

Objectives: To present an application of specification curve analysis-a novel analytic method that involves defining and implementing all plausible and valid analytic approaches for addressing a research question-to nutritional epidemiology.

Study Design And Setting: We reviewed all observational studies addressing the effect of red meat on all-cause mortality, sourced from a published systematic review, and documented variations in analytic methods (eg, choice of model, covariates, etc.).

Assessing the genetic contribution of cumulative behavioral factors associated with longitudinal type 2 diabetes risk highlights adiposity and the brain-metabolic axis.

While genetic factors, behavior, and environmental exposures form a complex web of interrelated associations in type 2 diabetes (T2D), their interaction is poorly understood. Here, using data from ~500K participants of the UK Biobank, we identify the genetic determinants of a "polyexposure risk score" (PXS) a new risk factor that consists of an accumulation of 25 associated individual-level behaviors and environmental risk factors that predict longitudinal T2D incidence. PXS-T2D had a non-zero heritability (h = 0.

Decoding the exposome: data science methodologies and implications in exposome-wide association studies (ExWASs).

This paper explores the exposome concept and its role in elucidating the interplay between environmental exposures and human health. We introduce two key concepts critical for exposomics research. Firstly, we discuss the joint impact of genetics and environment on phenotypes, emphasizing the variance attributable to shared and nonshared environmental factors, underscoring the complexity of quantifying the exposome's influence on health outcomes.

DNA characterization reveals potential operon-unit packaging of extracellular vesicle cargo from a gut bacterial symbiont.

Extracellular vesicles (EVs) are lipid bilayer-bound entities secreted by cells across all domains of life, known to contain a range of components, including protein complexes, RNA, and DNA. Recent studies on microbial extracellular vesicles indicate that these virus-sized nanoparticles, 40-90nm in diameter, readily cross the epithelial barrier and reach systemic circulation, can be detected in tissues throughout the body in mice and that 1mL of plasma from healthy humans contains up to one million bacterial EVs. They have been recently recognized for their biologically functional roles, including modulation of bacterial physiology and host-microbe interactions, hence their gain in the microbiome research community's attention.

Prediction and stratification of longitudinal risk for chronic obstructive pulmonary disease across smoking behaviors.

Smoking is the leading risk factor for chronic obstructive pulmonary disease (COPD) worldwide, yet many people who never smoke develop COPD. We perform a longitudinal analysis of COPD in the UK Biobank to derive and validate the Socioeconomic and Environmental Risk Score which captures additive and cumulative environmental, behavioral, and socioeconomic exposure risks beyond tobacco smoking. The Socioeconomic and Environmental Risk Score is more predictive of COPD than smoking status and pack-years.

Pediatric and Young Adult Household Transmission of the Initial Waves of SARS-CoV-2 in the United States: Administrative Claims Study.

Background: The correlates responsible for the temporal changes of intrahousehold SARS-CoV-2 transmission in the United States have been understudied mainly due to a lack of available surveillance data. Specifically, early analyses of SARS-CoV-2 household secondary attack rates (SARs) were small in sample size and conducted cross-sectionally at single time points. From these limited data, it has been difficult to assess the role that different risk factors have had on intrahousehold disease transmission in different stages of the ongoing COVID-19 pandemic, particularly in children and youth.

Association between timing and consistency of physical activity and type 2 diabetes: a cohort study on participants of the UK Biobank.

Aims/hypothesis: We sought to quantify the relationship between morning, afternoon or evening physical activity and consistency (e.g. routine) and risk of type 2 diabetes.

Spatio-temporal interpolation and delineation of extreme heat events in California between 2017 and 2021.

Robust spatio-temporal delineation of extreme climate events and accurate identification of areas that are impacted by an event is a prerequisite for identifying population-level and health-related risks. In prior research, attributes such as temperature and humidity have often been linearly assigned to the population of the study unit from the closest weather station. This could result in inaccurate event delineation and biased assessment of extreme heat exposure.