Julie E Buring's research while affiliated with Brigham and Women's Hospital and other places

Publications (975)

Article
Background: Vitamin D supplements are widely recommended for bone health in the general population, but data on whether they prevent fractures have been inconsistent. Methods: In an ancillary study of the Vitamin D and Omega-3 Trial (VITAL), we tested whether supplemental vitamin D3 would result in a lower risk of fractures than placebo. VITAL w...
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Importance: Results of several small randomized clinical trials have suggested that supplements of marine ω-3 fatty acids may be beneficial in treating signs and symptoms of dry eye disease (DED). However, randomized clinical trial data to examine whether ω-3 fatty acid supplements can prevent DED are lacking. Objective: To evaluate whether long...
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Background Short-term randomized trials suggest that a 500 mg/day vitamin C supplement reduces serum urate, while observational studies show vitamin E is inversely associated with gout risk. Objective We evaluated the effect of supplemental vitamin C (pre-specified primary exposure) and vitamin E (pre-specified secondary exposure) on new diagnoses...
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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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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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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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Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic component...
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Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use¹. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels², heart disease remains the leading cause of death worldwi...
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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...
Preprint
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Genetic variants within nearly 1,000 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. To expand our understanding of the underl...
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A major challenge of genome-wide association studies (GWAS) 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 firs...
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Age at first sexual intercourse and age at first birth have implications for health and evolutionary fitness. In this genome-wide association study (age at first sexual intercourse, N = 387,338; age at first birth, N = 542,901), we identify 371 single-nucleotide polymorphisms, 11 sex-specific, with a 5–6% polygenic score prediction. Heritability of...
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High intake of marine omega‐3 (n‐3) fatty acids has been associated with lower risk of cognitive decline; however, few large‐scale, long‐term randomized trials have been conducted. We evaluated n‐3 supplementation (1 gram/day, including 840 mg of EPA + DHA) and change in cognitive function over 2‐3 years. Community‐dwelling participants aged 60+ ye...
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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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Introduction: Insulin resistance is central to the development of type 2 diabetes (T2D). Association between specific biomarkers of glucose-insulin homeostasis and T2D have been inconsistent. Whether vitamin D or omega-3 fatty acids (n-3 FA) can modify these associations is also unclear. Hypothesis: We hypothesized that higher insulin, C-peptide, i...
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Context The effect of daily vitamin D supplementation on the serum concentration of vitamin D (the parent compound) may offer insight into vitamin D disposition. Objective To assess the total serum vitamin D response to vitamin D3 supplementation and whether it varies according to participant characteristics. To compare results with corresponding...
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Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-c...
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Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of Europe...
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Background: While physical activity has consistently been associated with decreased mortality rates, it remains unknown if there is a single "ideal" combination of time in physical activities of different intensities and sedentary behavior (SB) associated with the lowest rate. This study examined the associations of combinations of time in moderat...
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Backgrounds - Branched-chain amino acids (BCAAs; isoleucine, leucine and valine) correlate with insulin resistance and poor glucose control, which may in part explain associations between type 2 diabetes (T2D) and cardiovascular disease (CVD). However, the relationships of BCAAs with other cardiometabolic pathways, including inflammation and dyslip...
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Background Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. Objectives The objective of this study wa...
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Background: Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer. Methods: We conducted a pooled case-control study of 703 cases and 864 matched controls nested within five prospective coho...
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Aims: The aim of this study was to develop, validate, and illustrate an updated prediction model (SCORE2) to estimate 10-year fatal and non-fatal cardiovascular disease (CVD) risk in individuals without previous CVD or diabetes aged 40–69 years in Europe. Methods and results: We derived risk prediction models using individual-participant data from...
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Background: With the popularity of step counting and feasibility of accumulating physical activity (PA) through sporadic spurts (e.g., taking the stairs), the 2018 PA Guidelines Committee called for research to inform step-based PA recommendations by quantifying relationships between patterns of stepping and health. Purpose: To examine the relation...
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Introduction: While insomnia is associated with an increased risk of incident cardiovascular disease (CVD), its relationship with ideal cardiovascular health (ICH) is less certain. Given that sleep disturbances increase with age, we examined the relationship between insomnia symptoms and ICH in older women. Methods: Among women participating in the...
Article
Background: Circulating branched-chain amino acids (BCAAs) are associated with insulin resistance and higher risk of incident type 2 diabetes (T2D); however, despite their potential as a target for T2D prevention, upstream determinants of plasma BCAAs are largely unknown. Therefore, we investigated modifiable lifestyle factors in relation to plasma...
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Background The association of antenatal depression with adverse pregnancy, birth, and postnatal outcomes has been an item of scientific interest over the last decades. However, the evidence that exists is controversial or limited. We previously found that one in five women in Kuwait experience antenatal depressive symptoms. Therefore, the aim of th...
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The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)]...
Article
Importance Atrial fibrillation (AF) is the most common heart rhythm disturbance, continues to increase in incidence, and results in significant morbidity and mortality. The marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D have been reported to have both benefits and risks with respect to incident...
Article
Background and aims Data on the relation of egg consumption with risk of type 2 diabetes (T2D) and coronary heart disease (CHD) are limited and inconsistent. Few studies have controlled for overall dietary patterns in egg-T2D or egg-CHD analyses, and it is unclear whether any observed elevated risks of T2D and CHD with frequent egg consumption is r...
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Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We inv...
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Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative t...
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Aims/hypothesis Interventions that reduce inflammation may delay progression of microvascular and macrovascular complications in diabetes. We examined the effects of vitamin D3 and/or n-3 fatty acid supplementation vs placebo on 5 year changes in serum inflammatory and cardiac biomarkers in adults with type 2 diabetes. Methods This study reports p...
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Context Although observational studies show inverse associations between vitamin D status and body weight/adiposity, there are few large randomized controlled trials (RCTs) investigating this relationship. Objective To determine whether vitamin D3 supplementation lowers weight or improves body composition. Design The VITamin D and OmegA-3 TriaL (...
Preprint
Full-text available
Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. This genome-wide association study (GWAS) of 102,084 migraine cases and 771,257 controls identified 123 loci of which 86 are novel. The loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine su...
Preprint
Full-text available
Reproductive longevity is critical for fertility and impacts healthy ageing in women, yet insights into the underlying biological mechanisms and treatments to preserve it are limited. Here, we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in ~200,000 women of European ancestry...
Article
Background There is interest in whether supplements, including vitamin D and marine omega-3 (n-3) fatty acids, may be effective migraine prophylaxis. However, few studies have evaluated whether vitamin D or n-3 fatty acid supplementation may reduce migraine frequency or severity. Methods Participants in the VITamin D and OmegA-3 TriaL (VITAL) were...
Article
Background The link between nut consumption and cardiovascular (CV) mortality remains unclear. Objective: to examine whether nut consumption is associated with CV mortality and estimate the proportion of reduced risk of CV mortality explained by intermediate factors. Methods We studied 39,167 women from the Women’s Health Study; 28,034 provided bl...
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Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospecti...
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Whether vitamin D or marine omega-3 (n-3) fatty acid supplementation reduces risk of cancer or cardiovascular disease (CVD) in general populations at usual risk for these outcomes is relatively unexplored in randomized trials. The primary goal of the VITamin D and Omeg A-3 Tria L (VITAL), a nationwide, randomized, placebo-controlled, 2 × 2 factoria...
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Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 × 10⁻⁸), of which 32 were in new BP-associated loci...
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Importance Epidemiologic and trial data suggest that vitamin D supplementation may reduce metastatic cancer and cancer mortality, reflecting shared biological pathways. Objective To follow up on the possible reduction in cancer death in the Vitamin D and Omega-3 Trial (VITAL) with an evaluation of whether vitamin D reduces the incidence of advance...
Article
Introduction: Although religious attendance can act as a protective health factor likely through social support and inherent beliefs, little is known about the relationship between the frequency of religious attendance and ideal cardiovascular health (ICH), particularly in older women, many of whom attend religious activities. Methods: We utilized...
Article
Introduction: We previously observed that circulating branched-chain amino acids (BCAAs) were associated with a higher risk of cardiovascular disease (CVD). However, the relationships of BCAAs with other cardiometabolic pathways other than type 2 diabetes (T2D) are unclear, including inflammation, dyslipidemia, and impaired glucose metabolism. Hypo...
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Background: It is unclear if lipoprotein(a) cholesterol (LpaC), the cholesterol carried by Lpa, is associated with CVD similar to Lpa mass, and if omega-3 fatty acids (n-3 FA) modify risk. Methods: 13,175 participants of the VITAL trial (NCT01169259) had baseline LpaC measured by density-gradient ultracentrifugation and were examined for incident C...
Article
Importance: Observational studies suggest that higher intake or blood levels of vitamin D and marine ω-3 fatty acids may be associated with lower risks of age-related macular degeneration (AMD). However, evidence from randomized trials is limited. Objective: To evaluate whether daily supplementation with vitamin D3, marine ω-3 fatty acids, or bo...
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Omega-3 (n-3) treatment may lower cardiovascular risk, yet its effects on the circulating lipidome and relation to cardiovascular risk biomarkers are unclear. We hypothesized that n-3 treatment is associated with favorable changes in downstream fatty acids (FAs), oxylipins, bioactive lipids, clinical lipid and inflammatory biomarkers. We examined t...
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Obesity is a risk factor for > 13 cancer sites, although it is unknown whether there is a common mechanism across sites. Evidence suggests a role for impaired branched-chain amino acid (BCAAs; isoleucine, leucine, valine) metabolism in obesity, insulin resistance, and immunity; thus, we hypothesized circulating BCAAs may be associated with incident...
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Background Circulating branched chain amino acids (BCAA) are associated with cardiometabolic risk, although the mechanisms leading to their accumulation remain uncertain. Examining the relationship between fasting status, metabolic syndrome, and type 2 diabetes (T2D) with circulating BCAA levels may provide insights into their metabolic handling....
Article
Background and purpose Among stroke patients, low serum 25‐hydroxyvitamin D predicts poor outcomes. In mice, higher omega‐3 (n‐3) fatty acid intake diminishes brain damage after stroke. In this study, we tested whether vitamin D or n‐3 fatty acids supplementation prior to stroke reduces the risk of functional limitations and physical disability aft...
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Background: Whether circulating polyunsaturated fatty acids (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. Methods: We utilized data from genome-wide association studies wi...
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Importance Low levels of 25-hydroxyvitamin D have been associated with higher risk for depression later in life, but there have been few long-term, high-dose large-scale trials. Objective To test the effects of vitamin D3 supplementation on late-life depression risk and mood scores. Design, Setting, and Participants There were 18 353 men and wome...
Article
Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated varian...
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Blood pressure (BP) was inconsistently associated with migraine and the mechanisms of BP-lowering medications in migraine prophylaxis are unknown. Leveraging large-scale summary statistics for migraine (Ncases/Ncontrols = 59,674/316,078) and BP (N = 757,601), we find positive genetic correlations of migraine with diastolic BP (DBP, rg = 0.11, P = 3...
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Objective Knee pain from osteoarthritis is frequent in the adult population. Prior trials have had conflicting results concerning vitamin D’s therapeutic effects on knee pain and few trials have investigated marine omega‐3 fatty acids (n‐3 FA). Methods The double‐blind, placebo‐controlled VITamin D and OmegA‐3 TriaL (VITAL) randomized 25,871 U.S....
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Background: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. Methods: We conducted a gene-environment interaction (GxE) analysis including 8,255 cases and 11,...
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Importance Migraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear. Objective To estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors....
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Context It is unclear whether vitamin D supplementation reduces risk of falls, and results from randomized controlled trials (RCTs) are conflicting. Objective To determine whether 2000 IU/day of supplemental vitamin D3 decreases fall risk Design VITamin D and OmegA-3 TriaL (VITAL) is a double-blind, placebo-controlled RCT including 25,871 adults,...
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Background Gallbladder cancer (GBC) has a female predominance, although other biliary tract cancers (BTCs) such as extrahepatic and intrahepatic bile duct (EHBDC and IHBDC) and ampulla of Vater (AVC) have a male predominance. The role of female reproductive factors in BTC etiology remains unclear. Methods We pooled data from 19 studies of >1.5 mil...
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Intrahepatic cholangiocarcinoma (ICC) arises from cholangiocytes in the intrahepatic bile duct and is the second most common type of liver cancer. Cholangiocytes express both oestrogen receptor-α and -β, and oestrogens positively modulate cholangiocyte proliferation. Studies in women and men have reported higher circulating oestradiol is associated...
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Background Elevated triglyceride-rich lipoprotein (TRL) and small-dense low-density lipoprotein (sdLDL) particles are hallmarks of atherogenic dyslipidemia, and their cholesterol content is hypothesized to drive atherosclerotic risk. Prospective epidemiological data pertaining to cholesterol content of TRLs and sdLDL in primary prevention populatio...