JoAnn E Manson's research while affiliated with Brigham and Women's Hospital and other places

Publications (814)

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Background Weight at birth has been associated with the development of various adult diseases, but its association with mortality remains unclear. Methods We included 22,389 men from the Health Professionals Follow-up Study (1994-2018) and 162,231 women from the Nurses’ Health Study (1992-2018) and the Nurses’ Health Study II (1991-2019). The haza...
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Purpose of Review Clonal hematopoiesis of indeterminate potential (CHIP) has been identified as a novel cardiovascular risk factor. Here we review the relationship of lifestyle and environmental risk factors predisposing to somatic mutations and CHIP and provide an overview on age-related cardiovascular outcomes. Recent Findings CHIP has been asso...
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The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic i...
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Adiposity has been associated with several health conditions as well as timing of menopause. Prior epidemiologic studies on the association of adiposity and anti-Müllerian hormone (AMH) have been inconsistent. We evaluated the relations of anthropometric measures with AMH at two time periods in a subset of premenopausal participants in the Nurses'...
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Background Low birth weight has been associated with a greater risk of cardiovascular disease (CVD). However, the interaction between low birth weight and adult lifestyle factors on the risk of CVD remains unclear. Methods We included 20,169 men from the Health Professionals Follow-up Study (HPFS, 1986–2016), 52,380 women from the Nurses’ Health St...
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Aims: We analyzed whether the frequency of adding salt to foods was associated with the hazard of premature mortality and life expectancy. Methods and results: A total of 501 379 participants from UK biobank who completed the questionnaire on the frequency of adding salt to foods at baseline. The information on the frequency of adding salt to fo...
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The WHI (Women’s Health Initiative) enrolled 161,808 racially and ethnically diverse postmenopausal women, ages 50-79 years, from 1993 to 1998 at 40 clinical centers across the United States. In its clinical trial component, WHI evaluated 3 randomized interventions (menopausal hormone therapy; diet modification; and calcium/vitamin D supplementatio...
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Introduction Both osteoporosis and cardiovascular disease (CVD) increase in women after menopause. Estrogen deficiency is thought to be an underlying mechanism for both these conditions. Methods Healthy menopausal women (n = 374, age 42–58 years) underwent cardiac CT scans over four years as participants in the Kronos Early Estrogen Prevention Stu...
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Aims/hypothesis Plant-based diets, especially when rich in healthy plant foods, have been associated with a lower risk of type 2 diabetes. However, whether plasma metabolite profiles related to plant-based diets reflect this association was unknown. The aim of this study was to identify the plasma metabolite profiles related to plant-based diets, a...
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Interval breast cancer refers to cancer diagnosed after a negative screening mammogram and before the next scheduled screening mammogram. Interval breast cancer has worse prognosis than screening-detected cancer. Body mass index (BMI) influences the accuracy of mammography and overall postmenopausal breast cancer risk, yet how is obesity associated...
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OBJECTIVE Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. The aim of this study was to investigate the associations of protein intake with development of T2D and the potential mediating roles of T2D biomarkers. RESEARCH DESIGN AND METHODS We included 108,681 postmenopausal women without T2D at baseline fr...
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Background: Efficacy of vitamin D supplementation may vary by dosing strategies and adiposity. To address such heterogeneity, we performed a meta-analysis of randomised controlled trials of vitamin D supplementation and total cancer outcomes. Methods: PubMed and Embase were searched through January 2022. Summary relative risk (SRR) and 95% confi...
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Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and...
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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...
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Background Strong biologic rationale supports both vitamin D and marine omega-3 (n-3) fatty acids for prevention of autoimmune disease (AD). Within the randomized, double-blind, placebo-controlled VIT amin D and Omeg A -3 Tria L ( VITAL ), we tested the effects of these supplements on AD incidence. We previously reported results after 5.3 years of...
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Background Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of mutant hematopoietic stem cells, confers risk for multiple diseases of aging including hematologic cancer and cardiovascular disease. Whole-exome or genome sequencing can detect CHIP, but due to those assays’ high cost, most population studies have been...
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Background Recommended systolic blood pressure (SBP) targets often do not consider the relationship of low diastolic blood pressure (DBP) levels with cardiovascular disease (CVD) and all-cause mortality risk, which is especially relevant for older people with concurrent comorbidities. We examined the relationship of DBP levels to CVD and all-cause...
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Associations of estrogen-alone and estrogen plus progestin with breast cancer incidence and related mortality are reviewed from observational studies (The Collaborative Group on Hormonal Factors in Breast Cancer and The Million Women Study, 2019) and the Women’s Health Initiative’s (2020) two randomized trials evaluating conjugated equine estrogen...
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Objective: The relationships between cardiometabolic indices and cognition were examined in recently menopausal women. Methods: Cross-sectional analysis of baseline data from the KEEPS (Kronos Early Estrogen Prevention Study)-Cognitive ancillary study (n = 621). Cognitive performance was assessed by the Modified Mini Mental Status (3MS) score (p...
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Human genetic studies support an inverse causal relationship between leukocyte telomere length (LTL) and coronary artery disease (CAD), but directionally mixed effects for LTL and diverse malignancies. Clonal hematopoiesis of indeterminate potential (CHIP), characterized by expansion of hematopoietic cells bearing leukemogenic mutations, predispose...
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Introduction: : Few large, randomized trials have evaluated marine n-3 supplements and cognition in healthy older adults. Methods: : Healthy community-dwelling participants aged 60+ years (mean [standard deviation] = 70.9 [5.8] years) in VITAL (randomized trial of n-3 fats [1 g/day, including 840 mg of eicosapentaenoic acid + docosahexaenoic aci...
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A relatively high healthy lifestyle index (HLI) score, representing a healthy diet, participation in moderate to vigorous physical exercise, no smoking, low to no alcohol intake, and a normal body mass index, has been associated with a reduced risk of invasive breast cancer. However, no study has shown an association between the HLI and the risk of...
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Background Epidemiologic studies on the relationship between avocado intake and long‐term cardiovascular disease (CVD) risk are lacking. Methods and Results This study included 68 786 women from the NHS (Nurses’ Health Study) and 41 701 men from the HPFS (Health Professionals Follow‐up Study; 1986–2016) who were free of cancer, coronary heart dise...
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Objective: Research is limited regarding the predictive utility of the RAND-36 questionnaire and physical performance tests in relation to all-cause, cardiovascular disease (CVD), and total-cancer mortality in older women. Methods: Data on the RAND-36 questionnaire, gait speed, and chair stand performance were assessed in 5,534 women aged ≥ 65 y...
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Background and aim Iron deficiency is associated with increased morbidity and mortality in older adults. However, data on its prevalence and incidence among older adults is limited. The aim of this study was to investigate the prevalence and incidence of iron deficiency in European community-dwelling older adults aged ≥ 70 years. Methods Secondary...
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Background Studies of diet and chronic disease include a recent important focus on dietary patterns. Patterns are typically defined by listing dietary variables, and by totaling scores that reflect whether consumption is encouraged or discouraged for listed variables. However, precision may be improved by including total energy consumption among th...
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Background: Circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are strongly associated with higher risk of incident type 2 diabetes (T2D); however determinants of elevated fasting levels are largely unknown. Objective: We aimed to characterize the modifiable lifestyle factors related to plasma BCAAs. Methods: We pe...
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Red blood cell (RBC) fatty acid (FA) patterns are becoming recognized as long-term biomarkers of tissue FA composition, but different analytical methods have complicated inter-study and international comparisons. Here we report RBC FA data, with a focus on the Omega-3 Index (EPA + DHA in % of total FAs in RBC), from samples of seven countries (USA,...
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Objectives Our primary aim was to evaluate whether prevalent type 2 diabetes (T2D) modifies the effects of omega-3 supplementation on heart failure (HF) hospitalization. Our secondary aim was to examine if race modifies the effects of omega-3 supplements on HF risk. Background It is unclear whether race and T2D modify the effects of omega-3 supple...
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Introduction: The relationship between artificially sweetened beverage (ASB) intake and type 2 diabetes (T2D) risk remains inconclusive. Few studies have evaluated whether circulating metabolites that reflect ASB consumption may unveil potential mechanisms underlying the association between ASB consumption and T2D risk. Hypothesis: We hypothesized...
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Introduction Although insufficient or prolonged sleep duration is associated with cardiovascular disease, sleep duration is not included in most lifestyle scores. This study evaluates the relationship between a lifestyle score, including sleep duration and cardiovascular disease risk. Methods A prospective analysis among 67,250 women in the Nurses...
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Background Prior studies suggested lower risk of heart failure (HF) in individuals taking H 2 receptor antagonists (H2RA) compared with H2RA nonusers in relatively small studies. We evaluated the association of H2RA use and incident HF in postmenopausal women in the large‐scale WHI (Women’s Health Initiative) study. Methods and Results This study...
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OBJECTIVE Trans fatty acids (TFAs) have harmful biologic effects that could increase the risk of type 2 diabetes (T2D), but evidence remains uncertain. We aimed to investigate the prospective associations of TFA biomarkers and T2D by conducting an individual participant-level pooled analysis. RESEARCH DESIGN AND METHODS We included data from an in...
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Background Higher physical activity levels are associated with lower breast cancer-specific mortality. In addition, the metabolic syndrome is associated with higher breast cancer-specific mortality. Whether the physical activity association with breast cancer mortality is modified by number of metabolic syndrome components (cardiometabolic risk fac...
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Background: Late-life exposure to ambient air pollution is a modifiable risk factor for dementia, but epidemiological studies have shown inconsistent evidence for cognitive decline. Air quality (AQ) improvement has been associated with improved cardiopulmonary health and decreased mortality, but to the best of our knowledge, no studies have examin...
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Importance: Social isolation and loneliness are increasing public health concerns and have been associated with increased risk of cardiovascular disease (CVD) among older adults. Objective: To examine the associations of social isolation and loneliness with incident CVD in a large cohort of postmenopausal women and whether social support moderat...
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Exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) have been associated with the emergence of depressive symptoms in older adulthood, although most studies used cross-sectional outcome measures. Elucidating the brain structures mediating the adverse effects can strengthen the causal role between air pollution and increasing dep...
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Late-life ambient air pollution is a risk factor for brain aging, but it remains unknown if improved air quality (AQ) lowers dementia risk. We studied a geographically diverse cohort of older women dementia free at baseline in 2008 to 2012 ( n = 2,239, aged 74 to 92). Incident dementia was centrally adjudicated annually. Yearly mean concentrations...
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Background We recently developed protein and carbohydrate intake biomarkers using metabolomics profiles in serum and urine, and used them to correct self-reported dietary data for measurement error. Biomarker-calibrated carbohydrate density was inversely associated with chronic disease risk, while protein density associations were mixed. Objective...
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Importance Marine omega-3 fatty acid (omega-3) supplements have been used to treat depression but their ability to prevent depression in the general adult population is unknown. Objective To test effects of omega-3 supplementation on late-life depression risk and mood scores. Design, Setting, and Participants A total of 18 353 adults participated...
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STUDY QUESTION Are menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk? SUMMARY ANSWER Irregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers. WHAT IS KNOWN ALREADY Long and irregular mens...
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Importance Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps. Objective To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs r...
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Objective: We examined lifestyle factors with midlife weight change according to history of gestational diabetes mellitus (GDM) in a large longitudinal female cohort. Research design and methods: In the Nurses' Health Study II, we categorized changes in lifestyle within 4-year periods and estimated their associations with concurrent changes in b...
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Objective: Oral contraceptives (OCs) and tubal ligation are commonly used methods of contraception that may impact ovarian function. Few studies have examined the association of these factors with antimüllerian hormone (AMH), a marker of ovarian aging. Methods: We examined the association of OC use and tubal ligation with AMH in the Nurses' Heal...
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Background Vitamin D may have a role in immune responses to viral infections. However, data on the association between vitamin D and SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) severity have been limited and inconsistent. Objective We examined the associations of predicted vitamin D status and intake with risk of SARS-CoV-2 infect...
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DNA methylation‐based epigenetic age acceleration (AgeAccel), an aging biomarker indicating faster biological aging relative to chronological age, is associated with many age‐related phenotypes. Blood‐based AgeAccel has been associated with lower cognitive function in several studies. However, there are limited data on associations of AgeAccel with...
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Background Cardiovascular health (CVH) has been defined by the American Heart Association (AHA) as the presence of the “Life’s Simple 7” ideal lifestyle and clinical factors. CVH is known to predict longevity and freedom from cardiovascular disease, the leading cause of death for women in the United States. DNA methylation markers of aging have bee...
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Genome‐wide DNA methylation assay (DNAm) reflects epigenetic aging and differences in gene expression, and may help to elucidate the role of systemic aging in cognitive decline. Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and may increase the risk of progression to dementia. However, few investigations have address...
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Low vitamin D levels have been associated with cognitive decline; however, few randomized trials have been conducted. In a trial, we evaluated vitamin D3 supplementation on cognitive decline. We included participants aged 60+ years (mean[SD] = 70.9[5.8] years) free of cardiovascular disease and cancer in two substudies in the VITAL 2 × 2 randomized...
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Background: SNPs associated with C-reactive protein (CRP) and plasma lipids have been investigated for polygenic overlap with Alzheimer's disease (AD) risk SNPs. Previously, we reported pleiotropic effects between SNPs associated with cognitive impairment (CI) and SNPs associated with systemic inflammation as measured by CRP and plasma lipids in t...
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Background and Purpose Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease–related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replic...
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Aims/hypothesisMenstrual cycle dysfunction has been associated with many endocrine-related diseases, but evidence linking menstrual cycle dysfunction with gestational diabetes mellitus (GDM) is scant. The current study investigated the association of pre-pregnancy menstrual cycle regularity and length during adolescence, early adulthood and mid-adu...
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Objectives To determine associations between geographic region and late-life depression (LLD) severity, item-level symptom burden, and treatment; to evaluate whether racial/ethnic disparities in LLD, previously observed in the overall sample, vary by region. Methods We included 25,502 VITAL (Vitamin D and Omega-3 Trial) participants and administer...
Conference Paper
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Background Omega-3 fatty acid-derived ‘specialized pro-resolving mediators’ (SPM) are low-abundance lipid mediators (LM) central to inflammation resolution. We investigated whether fish oil (FO) supplementation was associated with pro-inflammatory and pro-resolving LM in patients with SLE compared to matched controls. Methods Within the Mass Gener...
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Aims The aim of this study was to explore the association of pregnancy loss (PL) with the incidence of cardiovascular disease (CVD) and examine the extent to which this relation is mediated by subsequent metabolic disorders. Methods and results We followed 95 465 ever-gravid women participating in the Nurses’ Health Study II between 1993 and 2017....
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The objective of this study was to determine the association between birthweight and risk of thyroid and autoimmune conditions in a large sample of postmenopausal women. Baseline data from the Women’s Health Initiative (n = 80,806) were used to examine the associations between birthweight category (<6 lbs., 6–7 lbs. 15 oz, 8–9 lbs. 15 oz, and ≥10 l...
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Background Assessing estimated sodium (Na) and potassium (K) intakes derived from 24-h urinary excretions versus a spot urine sample if comparable could reduce participant burden in epidemiologic and clinical studies. Objectives In a two-week controlled feeding study, Na and K excretion from a 24-h urine collection were compared with a first void...
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Background: Identification of factors that may help to preserve cognitive function in late life could elucidate mechanisms and facilitate interventions to improve the lives of millions of people. However, the large number of potential factors associated with cognitive function poses an analytical challenge. Objective: We used data from the longi...
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Background: Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine omega-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose related. Methods: The MEDLINE and Embase databases were...
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Background Observational studies among older women have associated vitamin D insufficiency with greater prevalence and incidence of urinary incontinence than older women with adequate vitamin D status. Less is known about the effect of vitamin D supplementation on reducing incontinence. Objective To evaluate the effects of vitamin D supplementatio...
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Background: Dietary patterns promoting hyperinsulinemia and chronic inflammation, including the empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP), have been shown to strongly influence risk of weight gain, type 2 diabetes, cardiovascular disease, and cancer. EDIH was developed using plasma C-pepti...
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Background Emerging evidence has linked sleep behaviors with the risk of cardiac arrhythmias. The various sleep behaviors are typically correlated; however, most of the previous studies only focused on the individual sleep behavior, without considering the overall sleep patterns. Objectives The purpose of this study was to prospectively investigat...
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Several forms of chronic distress including anxiety and depression are associated with adverse cardiometabolic outcomes. Metabolic alterations may underlie these associations. Whether these forms of distress are associated with metabolic alterations even after accounting for comorbid conditions and other factors remains unclear. Using an agnostic a...
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Background Observational studies have suggested associations of vitamin D deficiency (VDD) with respiratory tract infections, impaired bone health, and myriad chronic diseases. Objective To assess potential causal relationships between vitamin D supplementation and a reduced risk of these conditions, a review of the evidence across available meta-...
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Background: Atrial fibrillation (AF) is associated with substantial morbidity and mortality. Short-term exposures to air pollution have been associated with AF triggering; less is known regarding associations between long-term air pollution exposures and AF incidence. Objectives: Our objective was to assess the association between long-term expo...
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Objective To evaluate the association between parity and breastfeeding and anti-Müllerian hormone levels (AMH) and change in AMH levels over time. Furthermore, we examined whether AMH levels mediate the relation of parity and breastfeeding with age at menopause. Study design Observational, prospective cohort study. Main outcome measures AMH level...
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Background: Anthropometric measures, including obesity, are important risk factors for breast and endometrial cancers in postmenopausal women. It is unknown whether these risk factors are associated with androgen metabolism, another risk factor for these cancers. Methods: Using baseline data from 1,765 postmenopausal women in the Women's Health...
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Background Epigenetic age acceleration (AgeAccel), which indicates faster biological aging relative to chronological age, has been associated with lower cognitive function. However, the association of AgeAccel with mild cognitive impairment (MCI) or dementia is not well-understood. We examined associations of four AgeAccel measures with incident MC...