Susan Redline's research while affiliated with Beth Israel Deaconess Medical Center and other places

Publications (1,000)

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Ever larger Structural Variant (SV) catalogs highlighting the diversity within and between populations help researchers better understand the links between SVs and disease. The identification of SVs from DNA sequence data is non-trivial and requires a balance between comprehensiveness and precision. Here we present a catalog of 355,667 SVs (59.34%...
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Despite the critical importance of attention for children's self-regulation and mental health, there are few task-based measures of this construct appropriate for use across a wide childhood age range including very young children. Three versions of a combined go/no-go and continuous performance task (GNG/CPT) were created with varying length and t...
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Study objectives: To assess whether the association between insomnia and subclinical myocardial injury, as measured by cardiac troponin T (cTnT), differs across insomnia phenotypes. Methods: We measured cTnT in 2188 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study who had completed sleep questionnaires and undergone unatten...
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Background Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results To expand our understa...
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Meta-analysis of whole genome sequencing/whole exome sequencing (WGS/WES) studies provides an attractive solution to the problem of collecting large sample sizes for discovering rare variants associated with complex phenotypes. Existing rare variant meta-analysis approaches are not scalable to biobank-scale WGS data. Here we present MetaSTAAR, a po...
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Study objectives: To assess the association between psychotropic medications and sleep microstructure in large community-based cohorts of older people. Methods: We analyzed overnight polysomnograms of 381 women from the Study of Osteoporotic Fractures (SOF) and 2,657 men from the Osteoporotic Fractures in Men Sleep Study (MrOS), who either used...
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Profiles of sleep duration and timing and corresponding electroencephalographic activity reflect brain changes that support cognitive and behavioral maturation and may provide practical markers for tracking typical and atypical neurodevelopment. To build and evaluate a sleep-based, quantitative metric of brain maturation, we used whole-night polyso...
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Background: Insomnia or poor sleep quality with objective short sleep duration (hereafter referred to as ISSD) has been identified as a high-risk phenotype among middle-aged persons. We evaluated the prevalence and clinical correlates of ISSD among community-living older persons. Methods: In 3053 men from the Osteoporotic Fractures in Men Sleep...
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Study Objectives Shift work is a risk factor for cardiometabolic disease, possibly through effects on sleep-wake rhythms. We hypothesized that evening (afternoon and night combined) and irregular (irregular/on-call or rotating combined) shift work during pregnancy is associated with increased odds of preeclampsia, preterm birth, and gestational dia...
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Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the...
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Introduction Moderate-Severe Obstructive Sleep Apnea (OSA, AHI>15) disturbs sleep through frequent bouts of apnea and is associated with daytime sleepiness. However, many individuals without moderate or severe OSA (i.e. AHI≤15) also report sleepiness. We propose that sleepiness may be a consequence of substantial flow limitation, even in the absenc...
Preprint
Mosaic mutations in blood are common with increasing age and are prognostic markers for cancer, cardiovascular dysfunction and other diseases. This group of acquired mutations include megabase-scale mosaic chromosomal alterations (mCAs). These large mutations have mainly been surveyed using SNP array data from individuals of European (EA) or Japane...
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Purpose To further characterize the relationship between obstructive sleep apnea (OSA) and carotid atherosclerosis, we examined the structural and metabolic features of carotid plaque using hybrid 18-F-fluorodeoxyglucose (FDG) Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in the Multi-Ethnic Study of Atherosclerosis (MESA). Met...
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Rationale: Sleep apnea is the manifestation of key "endotypic traits" including greater pharyngeal collapsibility, reduced dilator muscle compensation and elevated chemoreflex loop gain. Objectives: We investigate how endotypic traits vary with obesity, age, sex, and race/ethnicity to influence sleep apnea disease severity (apnea-hypopnea index,...
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Background Although sufficient and healthy sleep is inversely associated with cardiovascular disease (CVD) and its risk factors, the American Heart Association's Life's Simple 7 (LS7), as a measure of cardiovascular health (CVH), did not include sleep. We evaluated an expanded measure of CVH that includes sleep as an eighth metric in relation to CV...
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Background: Sleep is fragmented by brief arousals, and excessive arousal burden has been linked to increased cardiovascular (CV) risk, but mechanisms are poorly understood. Research question: Do arousals trigger cardiac ventricular repolarisation lability that may predispose people to long-term cardiovascular mortality? Study design and methods...
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Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40–50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes¹. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 inde...
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We introduce the concept of cardiac neuroautonomic renewability and a method for its quantification. This concept refers to the involuntary nervous system's capacity to improve cardiac control in response to restorative interventions, such as sleep. We used the change in heart rate fragmentation (ΔHRF), before sleep onset compared to after sleep te...
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Background: The epithelial Na+ channel (ENaC) is intrinsically linked to fluid volume homeostasis and blood pressure. Specific rare mutations in SCNN1A, SCNN1B, and SCNN1G, genes encoding the α, β, and γ subunits of ENaC, respectively, are associated with extreme blood pressure phenotypes. No associations between blood pressure and SCNN1D, which e...
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Objectives Examine the associations of sleep measures with kidney function changes over time among individuals from a community-based study. Methods The sample includes 1657 participants (287 with chronic kidney disease [CKD]) in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (mean age: 57.7 years, male: 46.0%). We examined associations be...
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Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question su...
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Large-scale whole-genome sequencing studies have enabled analysis of noncoding rare-variant (RV) associations with complex human diseases and traits. Variant-set analysis is a powerful approach to study RV association. However, existing methods have limited ability in analyzing the noncoding genome. We propose a computationally efficient and robust...
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Background Obstructive sleep apnea (OSA) and its features, such as chronic intermittent hypoxia, may differentially affect specific molecular pathways and processes in the pathogenesis of coronary artery disease (CAD) and influence the subsequent risk and severity of CAD events. In particular, competing adverse (eg, inflammatory) and protective (eg...
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The 1/f spectral slope of the electroencephalogram (EEG) estimated in the γ frequency range has been proposed as an arousal marker that differentiates wake, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Here, we sought to replicate and extend these findings in a large sample, providing a comprehensive characterization of h...
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Background: Inflammation-related mechanisms may be important in the development of obstructive sleep apnea (OSA), and diet plays a crucial role in modulating inflammation. Current epidemiologic evidence for the associations between dietary patterns and OSA risk is limited to cross-sectional studies. Objectives: We investigated prospectively the...
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Background: Evaluation and interpretation of the literature on obstructive sleep apnea is needed to consolidate and summarize key factors important for clinical management of the OSA adult patient. Toward this goal, an international collaborative of multidisciplinary experts in sleep apnea evaluation and treatment have produced the International C...
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Unresolved obstructive sleep apnoea (OSA) after an adenotonsillectomy, henceforth referred to as persistent OSA, is increasingly recognised in children (2–18 years). Although associated with obesity, underlying medical complexity, and craniofacial disorders, persistent OSA also occurs in otherwise healthy children. Inadequate treatment of persisten...
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Obstructive sleep apnea (OSA), in which breathing is reduced or ceased during sleep, affects at least 10% of the population and is associated with numerous comorbidities. Current clinical diagnostic approaches characterize severity and treatment eligibility using the average respiratory event rate over total sleep time (apnea hypopnea index). This...
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Study objectives We evaluated if self-reported sleepiness was associated with neuroimaging markers of brain aging and ischemic damage in a large community-based sample. Methods Participants from the Framingham Heart Study Offspring cohort (n=468, 62.5±8.7, 49.6%M) free of dementia, stroke, and neurological diseases, completed sleep questionnaires...
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The general public increasingly adopts smart wearable devices to quantify sleep characteristics and dedicated devices for sleep assessment. The rapid evolution of technology has outpaced the ability to implement validation approaches and demonstrate relevant clinical applicability. There are untapped opportunities to validate and refine consumer de...
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Objective To describe daytime sleepiness and insomnia among adults in Samoa and identify modifiable factors associated with these measures. Design/setting Cross-sectional analysis of data from the Soifua Manuia (“Good Health”) study (n=519, 55.1% female); Upolu island, Samoa. Methods Daytime sleepiness and insomnia were assessed with the Epworth...
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Sleep-disordered breathing (SDB), characterized by specific underlying physiological mechanisms, comprises obstructive and central pathophysiology, affects nearly 1 billion individuals worldwide, and is associated with excessive cardiopulmonary morbidity. Strong evidence implicates SDB in cardiac arrhythmogenesis. Immediate consequences of SDB incl...
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Objectives This analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (Sunosi™) 37.5 (OSA only), 75, 150, or 300 mg/d. Methods In two 12-week, randomized, placebo-controlled trials and one 1-year open-label extension study, changes in weight were evaluated from baseline...
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A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We fir...
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Integrating genetic information with metabolomics has provided new insights into genes affecting human metabolism. However, gene-metabolite integration has been primarily studied in individuals of European Ancestry, limiting the opportunity to leverage genomic diversity for discovery. In addition, these analyses have principally involved known meta...
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Introduction: Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epi-demiologic evidence supporting the importance of genetic factors influencing OSA, but limited data implicating specific genes. Methods: Leveraging high dep...
Preprint
Background Sleep Disordered Breathing (SDB) is characterized by repeated breathing reductions or cessations during sleep, often accompanied by oxyhemoglobin desaturation. How SDB affects the molecular environment is still poorly understood. Methods We studied the association of three SDB measures: the Apnea Hypopnea Index (AHI), average and minimu...
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Full-text available
Background Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods Between January 2019 and June 2020 we distributed a web-based 12-question sur...
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Rationale: Genetic variation has a substantial contribution to chronic obstructive pulmonary disease (COPD) and lung function measurements. Heritability estimates using genome-wide genotyping data can be biased if analyses do not appropriately account for the non-uniform distribution of genetic effects across the allele frequency and linkage diseq...
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Study objectives: Obstructive sleep apnea (OSA) is characterized by multiple "endotypic traits", including pharyngeal collapsibility, muscle compensation, loop gain, and arousal threshold. Here we examined 1) within-night repeatability, 2) long-term consistency, and 3) influences of body position and sleep state, of endotypic traits estimated from...
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Study Objectives Periodic Limb Movement in Sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a Genome-Wide Association Study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of 4 cohorts (MrOS, th...
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Objectives: Insomnia is highly prevalent among persons with chronic pain. Although cognitive behavioral therapy for insomnia is recommended as first-line treatment for insomnia, it is underutilized. We tested the feasibility of a potentially scalable alternative - Brief Behavioral Therapy for Insomnia (BBTI) for former National Football League (NF...
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Background: The availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure. Methods: We conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision...
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In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS i...
Preprint
Objective To describe daytime sleepiness and insomnia among adults in Samoa and identify modifiable factors associated with these measures. Design/setting Cross-sectional analysis of data from the Soifua Manuia (“Good Health”) study (n=519, 55.1% female); Upolu island, Samoa. Methods Daytime sleepiness and insomnia were assessed with the Epworth...
Preprint
Full-text available
Background Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of upper airway obstruction during sleep resulting in oxygen desaturation and sleep fragmentation, and associated with increased risk of adverse health outcomes. Metabolites are being increasingly used for biomarker discovery and evaluation of disease...
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Introduction The 1/f spectral slope of the electroencephalogram (EEG) estimated in the gamma frequency range has been shown to reflect neural excitation/inhibition ratio and synchronization level within local neural populations. It was proposed as an arousal marker that differentiates wake, non-rapid eye movement (NREM) sleep, and rapid eye movemen...
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Introduction Sleep disturbances increase with age and are predictors of mortality. However, summary metrics typically derived in sleep clinics from gold standard clinical analysis of polysomnograms (PSGs) only represent a very small fraction of data collected. In this study, we designed deep neural networks that estimate age as a proxy for overall...
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Full-text available
Study Objectives Shift work is a risk factor for cardiometabolic disease, possibly through effects on sleep-wake rhythms. We hypothesized that shift work during pregnancy is associated with increased odds of preeclampsia, preterm birth, and gestational diabetes mellitus (GDM), and that the association is mediated by irregular sleep timing. Methods...
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Introduction Obstructive sleep apnea (OSA) may trigger inflammation. However, growing evidence suggests a role for inflammation in predisposing OSA through increased upper airway size/collapsibility and altered ventilatory control. Inflammation also promotes sleep disturbance and excessive daytime sleepiness (EDS). Genetic analysis may provide furt...
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Introduction Excessive daytime sleepiness (EDS) affects 10-20% of the population and is associated with cardiovascular diseases (CVD) and mortality. However, EDS is heterogeneous, associated with both short and long sleep duration. It is unclear whether each subtype is related to CVD. Methods To understand the association of EDS subtypes (stratifi...
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Introduction Prior research on the association of sleep with mortality has tended to focus on single sleep dimensions such as insufficiency. However, sleep health is conceptualized to consist of multiple inter-related dimensions: prior work suggests that simultaneous consideration of multiple sleep dimensions may better predict health outcomes than...
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Introduction The nucleotide-binding domain leucine rich family pyrin containing 3 (NLRP3) inflammasome protein complex activates caspase-1 to convert the pro-forms of IL-18 and IL-1 beta (IL-1β) into their active forms and is involved in homeostatic sleep and sleep responses to pathogenic stimuli. Intermittent hypoxia (IH) is a hallmark of sleep di...
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Introduction Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of upper airway obstruction during sleep resulting in oxygen desaturation and sleep fragmentation, and associated with increased risk of adverse health outcomes. Metabolites are being increasingly used for biomarker discovery and evaluation of diseas...
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Introduction We aim to determine if white matter hyperintensities and decreased brain volumes are associated with sleep-disordered breathing (SDB), in a diverse sample of middle-aged and older Hispanic/Latino adults. Methods Our sample of 1,119 Hispanics/Latinos (ages older than 50-years; 70% female) from the Hispanic Community Health Study/Study...
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Introduction The potential contributions of sleep apnea (SA) to the risk of developing many diseases remain unidentified due to survey limits in cohort studies. We aimed to identify novel associations between common comorbidities in participants with SA compared to matched controls in a clinical biobank by leveraging electronic health record (EHR)...
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Introduction Pediatric obstructive sleep apnea (OSA) disproportionately affects children from minority groups and children living in disadvantaged neighborhoods, but the risk factors that drive this risk are not well understood. We investigated the relationship between minority race/ethnicity, household risk factors (smoking, socio-economic status...
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Introduction Obstructive sleep apnea (OSA) is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. There is strong clinical and epidemiologic evidence supporting the importance of genetic factors influencing OSA, but limited data implicating specific genes. Methods Leveraging high depth ge...
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Introduction Most of the current automatic polysomnography sleep staging methods use multi-signal data and require a sequence of preceding and following epochs to score the stage of a specific epoch, which may not be desirable for analysis in real-time and/or in free-living conditions. We developed a deep learning-based sleep staging algorithm, nam...
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Introduction To identify actigraphy sleep health profiles in older men (Osteoporotic Fractures in Men Study; N=2,640) and women (Study of Osteoporotic Fractures; N=2.430), and to determine whether the identified profiles predict mortality. Methods We applied a novel and flexible clustering approach (Multiple Coalesced Generalized Hyperbolic mixtur...
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Introduction Obstructive sleep apnea (OSA) often co-occurs with other health outcomes. The respiratory event index (REI), often used to define OSA, is similarly correlated with several health phenotypes. Genetic data provide an opportunity to explain the nature of these associations. Methods We used data from the Hispanic Community Healthy Study/S...
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Introduction Many traditional sleep questionnaires were developed in younger populations and may have poor sensitivity to detect objective sleep deficiency in older persons due to atypical presentations, aging-related decreases in symptom awareness, and different expectations about health. Methods In a secondary analysis of data from the Osteoporo...
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We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci atta...
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Polygenic risk scores (PRSs) aggregate the effects of genetic variants across the genome and are used to predict risk of complex diseases, such as obesity. Current PRSs only include common variants (minor allele frequency (MAF) ≥1%), whereas the contribution of rare variants in PRSs to predict disease remains unknown. Here, we examine whether augme...
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Study objectives: The long-term effect of continuous positive airway pressure (CPAP) on 24-hour blood pressure (BP) in high-risk patients with obstructive sleep apnea (OSA) is uncertain. We aimed to determine the effect of CPAP treatment on ambulatory BP in individuals with moderate or severe OSA and cardiovascular disease (CVD) or multiple CVD ri...
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Objective: Chronic exposure to stress is associated with metabolic syndrome (MetS), but the mechanism is unclear. We investigated associations between chronic burden, sleep and MetS in the CARDIA Study. Methods: Chronic burden was self-reported (2000-2001) according to experiences with stressors for longer than 6 months. Wrist actigraphy-measure...
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Background: Rare sequence variation in genes underlying cardiac repolarization and common polygenic variation influence QT interval duration. However, current clinical genetic testing of individuals with unexplained QT prolongation is restricted to examination of monogenic rare variants. The recent emergence of large-scale biorepositories with sequ...
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Objective To characterize family and environmental correlates of sleep patterns that may contribute to differences in infant sleep. Methods We studied 313 infants in the Rise & SHINE (Sleep Health in Infancy & Early Childhood study) cohort. Our main exposures were the parent-reported sleep environment, feeding method and sleep parenting strategies...
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Socioeconomic status (SES) is a powerful determinant of health, as those with less resources across the lifespan have overall worse health outcomes with greater mortality and morbidity. SES has been associated with obstructive sleep apnea (OSA) outcomes, from diagnosis to treatment with continuous positive airway pressure (CPAP). Small observationa...
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While polygenic risk scores (PRSs) enable early identification of genetic risk for chronic obstructive pulmonary disease (COPD), predictive performance is limited when the discovery and target populations are not well matched. Hypothesizing that the biological mechanisms of disease are shared across ancestry groups, we introduce a PrediXcan-derived...
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Study Objectives Conventional metrics of sleep quantity/depth have serious shortcomings. Odds-Ratio-Product (ORP) is a continuous metric of sleep depth ranging from 0 (very deep sleep) to 2.5 (full-wakefulness). We describe an ORP-based approach that provides information on sleep disorders not apparent from traditional metrics. Methods We analysed...
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Objective: Caregivers frequently report poor quality of life (QOL) in children with sleep-disordered breathing (SDB). Our objective is to assess the correlation between caregiver- and child-reported QOL in children with mild SDB and identify factors associated with differences between caregiver and child report. Study design: Analysis of baselin...
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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 Resea...
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Study Objectives Obstructive sleep apnea has major health consequences but is challenging to treat. For many therapies, efficacy is determined by the severity of underlying pharyngeal collapsibility, yet there is no accepted clinical means to measure it. Here we provide insight into which polysomnographic surrogate measures of collapsibility are va...
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Background: Sleep irregularity has been linked to incident cardiovascular disease (CVD). Less is known about sleep regularity and associations with atherosclerosis. Our objective was to examine associations of sleep regularity with measures of atherosclerosis in the diverse MESA cohort. Methods: Participants from the MESA Sleep Study (2010-2013; N=...
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Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular...
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Background: Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive classes to achieve blood pressure (BP) control. The estimated prevalence of aTRH from population-based studies is ~12-15% among adults with hypertension (HTN). Individuals with aTRH have an increased risk for cardiovascular even...
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Objective: To examine the relationships between self-reported sleep characteristics and risk of incident vertebral fracture and hip fracture in women. Design: Longitudinal cohort study. Setting: Nurses' Health Studies (NHS: 2002-2014, NHSII: 2001-2015). Participants: Total 122,254 female registered nurses (46,129 NHS, 76,125 NHSII) without p...