Protein risk scores enable precise prediction of cardiovascular events in chronic kidney disease patients.

Background: Cardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). However, there is still a lack of reliable biomarkers to predict cardiovascular events (CVEs) in this population.

Methods: This study aimed to develop a protein risk score (ProRS) model to predict CVEs in CKD patients.

Large-scale evaluation of proteomic and polygenic risk scores reveals complementary contributions to incident disease prediction.

Plasma proteins capture dynamic physiological processes and may offer more immediate insight into disease risk than static genetic predictors. We evaluated the predictive utility of proteomic risk scores (ProRS) versus polygenic risk scores (PRS) across 301 phenotypes in 39,843 participants from the UK Biobank Pharma Proteomics Project. ProRS, trained on prevalent cases, were tested for incident disease and benchmarked against PRS derived from genome-wide association statistics.

Augmenting electronic health record data with social and environmental determinant of health measures to understand regional factors associated with asthma exacerbations.

Electronic health records (EHRs) provide rich data for diverse populations but often lack information on social and environmental determinants of health (SEDH) that are important for the study of complex conditions such as asthma, a chronic inflammatory lung disease. We integrated EHR data with seven SEDH datasets to conduct a retrospective cohort study of 6,656 adults with asthma. Using Penn Medicine encounter data from January 1, 2017 to December 31, 2020, we identified individual-level and spatially-varying factors associated with asthma exacerbations.

Developmental lead exposure and aggression in male rats: Influences of maternal care and environmental enrichment.

Developmental lead (Pb) exposure results in a variety of cognitive deficits and behavioral issues including increased antisocial behavior and aggression. This study investigated the effect of developmental Pb exposure on aggression and violent behavior in male rats and the potential modulatory influences of quality of maternal care and enriched/non-enriched housing conditions. Long-Evans male rats with or without Pb exposure (perinatal or early postnatal) from low or high maternal care mothers (based on amounts of licking/grooming and arched-back nursing) were randomly assigned to live in enriched or non-enriched environments at weaning.

Influences of quality of maternal care and environmental enrichment on associative memory function in rats with early life lead exposure.

Introduction: Children in low socioeconomic status (SES) communities are at higher risk of exposure to lead (Pb) and potentially more severe adverse outcomes from Pb exposures. While the factors encompassing SES are complex, low SES households often have less enriching home environments and parent-child interactions. This study investigated the extent to which environmental/behavioral factors (quality of maternal care and richness of the postnatal environment) may modify adverse effects from Pb exposure.

Aldo-keto reductase (AKR) superfamily website and database: An update.

The aldo-keto reductase (AKR) superfamily is a large family of proteins found across the kingdoms of life. Shared features of the family include 1) structural similarities such as an (α/β)-barrel structure, disordered loop structure, cofactor binding site, and a catalytic tetrad, and 2) the ability to catalyze the nicotinamide adenine dinucleotide (phosphate) reduced (NAD(P)H)-dependent reduction of a carbonyl group. A criteria of family membership is that the protein must have a measured function, and thus, genomic sequences suggesting the transcription of potential AKR proteins are considered pseudo-members until evidence of a functionally expressed protein is available.

Clarifying Chronic Obstructive Pulmonary Disease Genetic Associations Observed in Biobanks via Mediation Analysis of Smoking.

Varying case definitions of COPD have heterogenous genetic risk profiles, potentially reflective of disease subtypes or classification bias (e.g., smokers more likely to be diagnosed with COPD).

Genome-wide association study in minority children with asthma implicates DNAH5 in bronchodilator responsiveness.

Variability in response to short-acting β-agonists (e.g., albuterol) among patients with asthma from diverse racial/ethnic groups may contribute to asthma disparities.

REALGAR: a web app of integrated respiratory omics data.

Motivation: In the post genome-wide association study (GWAS) era, omics techniques have characterized information beyond genomic variants to include cell and tissue type-specific gene transcription, transcription factor binding sites, expression quantitative trait loci (eQTL) and many other biological layers. Analysis of omics data and its integration has in turn improved the functional interpretation of disease-associated genetic variants. Over 170 000 transcriptomic and epigenomic datasets corresponding to studies of various cell and tissue types under specific disease, treatment and exposure conditions are available in the Gene Expression Omnibus resource.

Gene-Based Analysis Reveals Sex-Specific Genetic Risk Factors of COPD.

Sex-specific differences have been noted among people with chronic obstructive pulmonary disease (COPD), but whether these differences are attributable to genetic variation is poorly understood. The availability of large biobanks with deeply phenotyped subjects such as the UK Biobank enables the investigation of sex-specific genetic associations that may provide new insights into COPD risk factors. We performed sex-stratified genome-wide association studies (GWAS) of COPD (male: 12,958 cases and 95,631 controls; female: 11,311 cases and 123,714 controls) and found that while most associations were shared between sexes, several regions had sex-specific contributions, including respiratory viral infection-related loci in/near C5orf56 and PELI1.

Multiomics analysis identifies BIRC3 as a novel glucocorticoid response-associated gene.

Background: Inhaled corticosteroid (ICS) response among patients with asthma is influenced by genetics, but biologically actionable insights based on associations have not been found. Various glucocorticoid response omics data sets are available to interrogate their biological effects.

Objective: We sought to identify functionally relevant ICS-response genetic associations by integrating complementary multiomics data sets.

Trait Insights Gained by Comparing Genome-Wide Association Study Results using Different Chronic Obstructive Pulmonary Disease Definitions.

Biobanks have facilitated the conduct of large-scale genomics studies, but they are challenged by the difficulty of validating some phenotypes, particularly for complex traits that represent heterogeneous groups ofpatients. The guideline definition of COPD, based on objective spirometry measures, has been preferred in genome-wide association studies (GWAS) conducted with epidemiological cohorts, but spirometry measures are seldom available for biobank participants. Defining COPD based on International Classification of Disease (ICD) codes or self-reported measures is highly feasible in biobanks, but it remains unclear whether the misclassification inherent in these definitions prevent the discovery of genetic variants that contribute to COPD.

Lung Function in African American Children with Asthma Is Associated with Novel Regulatory Variants of the KIT Ligand and Gene-By-Air-Pollution Interaction.

Baseline lung function, quantified as forced expiratory volume in the first second of exhalation (FEV), is a standard diagnostic criterion used by clinicians to identify and classify lung diseases. Using whole-genome sequencing data from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine project, we identified a novel genetic association with FEV on chromosome 12 in 867 African American children with asthma ( = 1.26 × 10, β = 0.

The influence of 15-week exercise training on dietary patterns among young adults.

Background/objectives: Little is currently known about how exercise may influence dietary patterns and/or food preferences. The present study aimed to examine the effect of a 15-week exercise training program on overall dietary patterns among young adults.

Subjects/methods: This study consisted of 2680 young adults drawn from the Training Intervention and Genetics of Exercise Response (TIGER) study.

Advanced Dietary Patterns Analysis Using Sparse Latent Factor Models in Young Adults.

Background: Principal components analysis (PCA) has been the most widely used method for deriving dietary patterns to date. However, PCA requires arbitrary ad hoc decisions for selecting food variables in interpreting dietary patterns and does not easily accommodate covariates. Sparse latent factor models can be utilized to address these issues.

Carriage of the V279F homozygous genotype, a rare allele, within the gene encoding Lp-PLA2 leads to changes in circulating intermediate metabolites in individuals without metabolic syndrome.

Aim: Identifying differences in plasma metabolic profiling between Lp-PLA2 279VV and 279FF in individuals without metabolic syndrome (MetS) can be used to elucidate the roles of novel Lp-PLA2 activities in normal physiological processes.

Methods: Non-MetS individuals with 279FF (n=36) and age-, sex- and BMI-matched VV subjects (n=36) were included in this analysis.

Results: The FF subjects exhibited no appreciable enzyme activity.