Interplay between lifestyle factors and polygenic risk for incident coronary heart disease in a large multiethnic cohort.

Introduction: The objective of this study was to examine the interplay of polygenic risk and individual lifestyle factors (and a composite score of lifestyle) as antecedents of CHD in a large multiethnic cohort.

Methods: We used Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort participants free of CHD at baseline (n = 60,568; 67 % female; 18 % non-European). The individual and joint associations of smoking, Mediterranean diet pattern, level of physical activity and polygenic risk with incident CHD were assessed using Cox regression adjusting for genetic ancestry and non-mediating risk factors.

Adherence to cardiovascular medications and risk of cardiovascular disease in breast cancer patients: A causal inference approach in the Pathways Heart Study.

Purpose: Women with breast cancer (BC) are at high risk of developing cardiovascular disease (CVD). We examined adherence to CVD medications and their association with major CVD events over 14 years of follow-up in the Pathways Heart Study, a prospective study of 4,776 stage I-III BC patients diagnosed from 2005-2013.

Methods: Eligibility included being alive 6 months post-BC diagnosis, with dyslipidemia, hypertension, or diabetes at diagnosis along with ≥1 prior outpatient order or dispensing for a statin, anti-hypertensive, or diabetes medication, respectively, in the 30 months prior.

Plasma Protein Profiling to Discern Indolent from Advanced Systemic Mastocytosis.

Mastocytosis is a heterogeneous disorder characterized by abnormal mast cell accumulation, in which the clinical severity may be explained by distinct molecular mechanisms. This study aimed to explore plasma protein biomarkers associated with systemic mastocytosis subtypes, as well as the cellular origin of the identified proteins. Plasma samples from patients with mastocytosis, including cutaneous mastocytosis (CM), indolent systemic mastocytosis (ISM), and advanced systemic mastocytosis (AdvSM), and a reference group of patients with polycythemia vera, were analyzed by Proximity Extension Assay technology targeting 275 proteins.

Identification of the Molecular Components of Enhancer-Mediated Gene Expression Variation in Multiple Tissues Regulating Blood Pressure.

Background: Inter-individual variation in blood pressure (BP) arises in part from sequence variants within enhancers modulating the expression of causal genes. We propose that these genes, active in tissues relevant to BP physiology, can be identified from tissue-level epigenomic data and genotypes of BP-phenotyped individuals.

Methods: We used chromatin accessibility data from the heart, adrenal, kidney, and artery to identify cis-regulatory elements (CREs) in these tissues and estimate the impact of common human single-nucleotide variants within these CREs on gene expression, using machine learning methods.

Polygenic risk and incident coronary heart disease in a large multiethnic cohort.

Objective: Many studies support the notion that polygenic risk scores (PRS) improve risk prediction for coronary heart disease (CHD) beyond conventional risk factors. However, PRS are not yet considered risk-enhancing factor in guidelines. Our objective was to determine the predictive performance of a commercially available PRS (CARDIO inCode-Score®) compared with the Pooled Cohorts Equations (PCE) in a contemporary, multi-ethnic cohort.

Characterization of Antibiotic-Resistance Antarctic That Produce Bacteriocin-like Compounds.

In this study, bacterial isolates C1-4-7, D2-4-6, and M1-4-11 from Antarctic soil were phenotypically and genotypically characterized, and their antibacterial spectrum and that of cell-free culture supernatant were investigated. Finally, the effect of temperature and culture medium on the production of antimicrobial compounds was investigated. The three bacteria were identified as different strains of the genus .

Sex-specific genetic architecture of blood pressure.

The genetic and genomic basis of sex differences in blood pressure (BP) traits remain unstudied at scale. Here, we conducted sex-stratified and combined-sex genome-wide association studies of BP traits using the UK Biobank resource, identifying 1,346 previously reported and 29 new BP trait-associated loci. Among associated loci, 412 were female-specific (P ≤ 5 × 10; P > 5 × 10) and 142 were male-specific (P ≤ 5 × 10; P > 5 × 10); these sex-specific loci were enriched for hormone-related transcription factors, in particular, estrogen receptor 1.

Temporal stability of fecal metabolomic profiles in irritable bowel syndrome.

Background: The potential of the fecal metabolome to serve as a biomarker for irritable bowel syndrome (IBS) depends on its stability over time. Therefore, this study aimed to determine the temporal dynamics of the fecal metabolome, and the potential relationship with stool consistency, in patients with IBS and healthy subjects.

Methods: Fecal samples were collected in two cohorts comprising patients with IBS and healthy subjects.

Asthma exacerbations and eosinophilia in the UK Biobank: a genome-wide association study.

Background: Asthma exacerbations reflect disease severity, affect morbidity and mortality, and may lead to declining lung function. Inflammatory endotypes ( T2-high (eosinophilic)) may play a key role in asthma exacerbations. We aimed to assess whether genetic susceptibility underlies asthma exacerbation risk and additionally tested for an interaction between genetic variants and eosinophilia on exacerbation risk.

Gut-Brain Axis Deregulation and Its Possible Contribution to Neurodegenerative Disorders.

The gut-brain axis is an essential communication pathway between the central nervous system (CNS) and the gastrointestinal tract. The human microbiota is composed of a diverse and abundant microbial community that compasses more than 100 trillion microorganisms that participate in relevant physiological functions such as host nutrient metabolism, structural integrity, maintenance of the gut mucosal barrier, and immunomodulation. Recent evidence in animal models has been instrumental in demonstrating the possible role of the microbiota in neurodevelopment, neuroinflammation, and behavior.

Asthma and COVID-19 Outcomes: A Prospective Study in a Large Health Care Delivery System.

Introduction: Previous studies on the outcomes of asthma and COVID-19 have shown inconsistent results. This study aimed to elucidate the association between asthma and COVID-19 outcomes.

Methods: We conducted a prospective study with a large health plan to compare the incidence of COVID-19 infection, hospitalization and ICU admission in a cohort of 41,282 patients with asthma and a 1:1 age-, sex-, and race-ethnicity-matched cohort without asthma across the following pandemic periods: pre-Delta (03/01/2020 to 05/31/2021), Delta (06/01/2021 to 12/31/2021), and Omicron (01/01/2022 to 08/13/2022).

Polygenic risk scores identify heterogeneity in asthma and chronic obstructive pulmonary disease.

Background: Asthma and chronic obstructive pulmonary disease (COPD) have distinct and overlapping genetic and clinical features.

Objective: We sought to test the hypothesis that polygenic risk scores (PRSs) for asthma (PRS) and spirometry (FEV and FEV/forced vital capacity; PRS) would demonstrate differential associations with asthma, COPD, and asthma-COPD overlap (ACO).

Methods: We developed and tested 2 asthma PRSs and applied the higher performing PRS and a previously published PRS to research (Genetic Epidemiology of COPD study and Childhood Asthma Management Program, with spirometry) and electronic health record-based (Mass General Brigham Biobank and Genetic Epidemiology Research on Adult Health and Aging [GERA]) studies.

Development of cardiometabolic risk factors following endocrine therapy in women with breast cancer.

Purpose: Studies comparing the effect of aromatase inhibitor (AI) and tamoxifen use on cardiovascular disease (CVD) risk factors in hormone receptor-positive breast cancer (BC) survivors report conflicting results. We examined associations of endocrine therapy use with incident diabetes, dyslipidemia, and hypertension.

Methods: The Pathways Heart Study examines cancer treatment exposures with CVD-related outcomes in Kaiser Permanente Northern California members with BC.

Development and application of an algorithm for statin-induced myopathy based on electronic health record-derived structured elements.

Objective: Considering the non-specific nature of muscle symptoms, studies of statin-induced myopathy (SIM) in electronic health records require accurate algortihms that can reliably identify true statin-related cases. However, prior algorithms have been constructed in study populations that preclude broad applicability. Here we developed and validated an algorithm that accurately defines SIM from electronic health records using structured data elements and conducted a study of determinants of SIM after applying the algorithm.

Neighborhood attributes and cardiovascular disease risk in breast cancer survivors: The Pathways Study.

Background: Breast cancer survivors are at a higher risk of cardiovascular disease (CVD) morbidity and mortality compared with the general population. The impact of objective social and built neighborhood attributes on CVD risk in a cohort of female breast cancer survivors was examined.

Methods: The 3975 participants came from the Pathways Study, a prospective cohort of women with invasive breast cancer from an integrated health care system in northern California.

Breast arterial calcification is associated with incident atrial fibrillation among older but not younger post-menopausal women.

Aims: The goal of this study was to examine the association of breast arterial calcification (BAC) presence and quantity with incident atrial fibrillation (AF) in a large cohort of post-menopausal women.

Methods And Results: We conducted a longitudinal cohort study among women free of clinically overt cardiovascular disease and AF at baseline (between October 2012 and February 2015) when they attended mammography screening. Atrial fibrillation incidence was ascertained using diagnostic codes and natural language processing.

Extracting patient-level data from the electronic health record: Expanding opportunities for health system research.

Background: Epidemiological studies of interstitial lung disease (ILD) are limited by small numbers and tertiary care bias. Investigators have leveraged the widespread use of electronic health records (EHRs) to overcome these limitations, but struggle to extract patient-level, longitudinal clinical data needed to address many important research questions. We hypothesized that we could automate longitudinal ILD cohort development using the EHR of a large, community-based healthcare system.

High-sensitivity troponin I is associated with cardiovascular outcomes but not with breast arterial calcification among postmenopausal women.

Background: Prior studies support the utility of high sensitivity troponin I (hsTnI) for cardiovascular disease (CVD) risk stratification among asymptomatic populations; however, only two prior studies examined women separately. The association between hsTnI and breast arterial calcification is unknown.

Methods: Cohort study of 2896 women aged 60-79 years recruited after attending mammography screening between 10/2012 and 2/2015.

Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids.

Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC ( = 6), UC ( = 6), IBS ( = 6) and healthy subjects ( = 6).

A large genome-wide association study of QT interval length utilizing electronic health records.

QT interval length is an important risk factor for adverse cardiovascular outcomes; however, the genetic architecture of QT interval remains incompletely understood. We conducted a genome-wide association study of 76,995 ancestrally diverse Kaiser Permanente Northern California members enrolled in the Genetic Epidemiology Research on Adult Health and Aging cohort using 448,517 longitudinal QT interval measurements, uncovering 9 novel variants, most replicating in 40,537 individuals in the UK Biobank and Population Architecture using Genomics and Epidemiology studies. A meta-analysis of all 3 cohorts (n = 117,532) uncovered an additional 19 novel variants.