Interaction of obesity polygenic score with lifestyle risk factors in an electronic health record biobank.

Background: Genetic and lifestyle factors have considerable effects on obesity and related diseases, yet their effects in a clinical cohort are unknown. This study in a patient biobank examined associations of a BMI polygenic risk score (PRS), and its interactions with lifestyle risk factors, with clinically measured BMI and clinical phenotypes.

Methods: The Mass General Brigham (MGB) Biobank is a hospital-based cohort with electronic health record, genetic, and lifestyle data.

Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.

Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples.

PUFA ω-3 and ω-6 biomarkers and sleep: a pooled analysis of cohort studies on behalf of the Fatty Acids and Outcomes Research Consortium (FORCE).

Background: n-3 and n-6 PUFAs have physiologic roles in sleep processes, but little is known regarding circulating n-3 and n-6 PUFA and sleep parameters.

Objectives: We sought to assess associations between biomarkers of n-3 and n-6 PUFA intake with self-reported sleep duration and difficulty falling sleeping in the Fatty Acids and Outcome Research Consortium.

Methods: Harmonized, de novo, individual-level analyses were performed and pooled across 12 cohorts.

The power of genetic diversity in genome-wide association studies of lipids.

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease.

Dose-response relationship between positive airway pressure therapy and excessive daytime sleepiness: the HomePAP study.

Study Objectives: The clinical benefits of positive airway pressure (PAP) therapy for obstructive sleep apnea are assumed to require adherent PAP usage, defined by the Centers for Medicare & Medicaid Services as ≥ 4 hours of use ≥ 70% of nights. However, this definition is based on early data and does not necessarily capture improvements at subthreshold adherence. We explored dose-response relationships between PAP adherence measures and excessive daytime sleepiness from the HomePAP randomized controlled trial.

Association of clonal hematopoiesis with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association of CHIP with COPD remains unclear.

Development and Psychometric Properties of the Sleep Parenting Scale for Infants.

Although infants' sleep behaviors are shaped by their interactions with parents at bedtime, few tools exist to capture parents' sleep parenting practices. This study developed a Sleep Parenting Scale for Infants (SPS-I) and aimed to (1) explore and validate its factorial structure, (2) examine its measurement invariance across mothers and fathers, and (3) investigate its reliability and concurrent and convergent validity. SPS-I was developed via a combination of items modified from existing scales and the development of novel items.

Informing sleep policy through field experiments.

Evidence is particularly needed from poorer communities.

Multidimensional sleep health in a diverse, aging adult cohort: Concepts, advances, and implications for research and intervention.

Purpose: To illustrate 2 frameshifts of multidimensional sleep health: i) use of composite sleep metrics; and ii) the correlations among sleep dimensions.

Participants: 735 adults of diverse backgrounds aged <65 years who participated in the Multi-Ethnic Study of Atherosclerosis.

Measures: In-home polysomnography, 7-day wrist actigraphy, and validated questionnaires.

Sleep apnea, coronary artery calcium density, and cardiovascular events: results from the Multi-Ethnic Study of Atherosclerosis.

Study Objectives: Evaluate the association between obstructive sleep apnea (OSA), coronary artery calcium (CAC) density, and cardiovascular events in the Multi-Ethnic Study of Atherosclerosis (MESA).

Methods: We analyzed 1,041 participants with nonzero CAC scores who had polysomnography and CAC density data from the fifth examination of the Multi-Ethnic Study of Atherosclerosis. OSA was defined as apnea-hypopnea index ≥ 15 events/h.

Sleep duration and vascular inflammation using hybrid positron emission tomography/magnetic resonance imaging: results from the Multi-Ethnic Study of Atherosclerosis.

Study Objectives: Short sleep duration (SD) is associated with cardiovascular disease. We investigated the relationship between objective SD and subclinical atherosclerosis employing hybrid positron emission tomography/magnetic resonance imaging with F-FDG tracer in the MESA cohort.

Methods: We utilized data from Multi-Ethnic Study of Atherosclerosis-SLEEP and Multi-Ethnic Study of Atherosclerosis-PET ancillary studies.

Prediction of Cognitive Decline Using Heart Rate Fragmentation Analysis: The Multi-Ethnic Study of Atherosclerosis.

Heart rate fragmentation (HRF), a new non-invasive metric quantifying cardiac neuroautonomic function, is associated with increasing age and cardiovascular disease. Since these are risk factors for cognitive decline and dementia, in the Multi-Ethnic Study of Atherosclerosis (MESA), we investigated whether disrupted cardiac neuroautonomic function, evidenced by increased HRF, would be associated with worse cognitive function assessed concurrently and at a later examination, and with greater cognitive decline. HRF was derived from the ECG channel of the polysomnographic recordings obtained in an ancillary study ( = 1,897) conducted in conjunction with MESA (2010-2012).

Racial-ethnic Differences in Actigraphy, Questionnaire, and Polysomnography Indicators of Healthy Sleep: The Multi-Ethnic Study of Atherosclerosis.

A paradigm shift in sleep science argues for a systematic, multidimensional approach to investigate sleep's association with disease and mortality and to address sleep disparities. We utilized the comprehensive sleep assessment of the Multi-Ethnic Study of Atherosclerosis (2010- 2013), a cohort of U.S.

Associations of sleep duration and sleep-wake rhythm with lung parenchymal abnormalities on computed tomography: The MESA study.

Impairment of the circadian rhythm promotes lung inflammation and fibrosis in pre-clinical models. We aimed to examine whether short and/or long sleep duration and other markers of sleep-wake patterns are associated with a greater burden of lung parenchymal abnormalities on computed tomography among adults. We cross-sectionally examined associations of sleep duration captured by actigraphy with interstitial lung abnormalities (n = 1111) and high attenuation areas (n = 1416) on computed tomography scan in the Multi-Ethnic Study of Atherosclerosis at Exam 5 (2010-2013).

Weekend night vs. school night sleep patterns, weight status, and weight-related behaviors among adolescents.

Objective: In this study, we examine associations between objectively measured weekend night vs. school night sleep patterns, weight status, and weight-related behaviors among adolescents.

Design: Cross-sectional study.

Whole-genome association analyses of sleep-disordered breathing phenotypes in the NHLBI TOPMed program.

Background: Sleep-disordered breathing is a common disorder associated with significant morbidity. The genetic architecture of sleep-disordered breathing remains poorly understood. Through the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we performed the first whole-genome sequence analysis of sleep-disordered breathing.

Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop.

Right ventricular dysfunction is a hallmark of advanced pulmonary vascular, lung parenchymal, and left heart disease, yet the underlying mechanisms that govern (mal)adaptation remain incompletely characterized. Owing to the knowledge gaps in our understanding of the right ventricle (RV) in health and disease, the National Heart, Lung, and Blood Institute (NHLBI) commissioned a working group to identify current challenges in the field. These included a need to define and standardize normal RV structure and function in populations; access to RV tissue for research purposes and the development of complex experimental platforms that recapitulate the environment; and the advancement of imaging and invasive methodologies to study the RV within basic, translational, and clinical research programs.

Sleep Disordered Breathing and Cardiovascular Disease: JACC State-of-the-Art Review.

Sleep disordered breathing causes repetitive episodes of nocturnal hypoxemia, sympathetic nervous activation, and cortical arousal, often associated with excessive daytime sleepiness. Sleep disordered breathing is common in people with, or at risk of, cardiovascular (CV) disease including those who are obese or have hypertension, coronary disease, heart failure, or atrial fibrillation. Current therapy of obstructive sleep apnea includes weight loss (if obese), exercise, and positive airway pressure (PAP) therapy.

Research Priorities in the Secondary Prevention of Atrial Fibrillation: A National Heart, Lung, and Blood Institute Virtual Workshop Report.

There has been sustained focus on the secondary prevention of coronary heart disease and heart failure; yet, apart from stroke prevention, the evidence base for the secondary prevention of atrial fibrillation (AF) recurrence, AF progression, and AF-related complications is modest. Although there are multiple observational studies, there are few large, robust, randomized trials providing definitive effective approaches for the secondary prevention of AF. Given the increasing incidence and prevalence of AF nationally and internationally, the AF field needs transformative research and a commitment to evidenced-based secondary prevention strategies.

BinomiRare: A robust test for association of a rare genetic variant with a binary outcome for mixed models and any case-control proportion.

Whole-genome sequencing (WGS) and whole-exome sequencing studies have become increasingly available and are being used to identify rare genetic variants associated with health and disease outcomes. Investigators routinely use mixed models to account for genetic relatedness or other clustering variables (e.g.

Rare Coding Variants Associated With Electrocardiographic Intervals Identify Monogenic Arrhythmia Susceptibility Genes: A Multi-Ancestry Analysis.

Background: Alterations in electrocardiographic (ECG) intervals are well-known markers for arrhythmia and sudden cardiac death (SCD) risk. While the genetics of arrhythmia syndromes have been studied, relations between electrocardiographic intervals and rare genetic variation at a population level are poorly understood.

Methods: Using a discovery sample of 29 000 individuals with whole-genome sequencing from Trans-Omics in Precision Medicine and replication in nearly 100 000 with whole-exome sequencing from the UK Biobank and MyCode, we examined associations between low-frequency and rare coding variants with 5 routinely measured electrocardiographic traits (RR, P-wave, PR, and QRS intervals and corrected QT interval).

Insomnia symptom severity and cognitive performance: Moderating role of APOE genotype.

Introduction: We evaluated whether insomnia symptom severity was associated with cognitive function, and whether this relationship was modified by biomarkers associated with Alzheimer's disease risk.

Methods: We examined insomnia symptoms and neuropsychological performance 3.4 years later in 511 dementia-free Framingham Heart Study participants (62.