Metabolomic profiles of an atherogenic TMAO-dietary pattern among postmenopausal women.

Purpose: We previously identified a dietary pattern (DP) associated with plasma trimethylamine -oxide (TMAO) and choline, the TMAO-DP, where higher scores represent more atherogenic potential of the diet. The mechanisms linking dietary intake to the presence of choline and TMAO in the plasma, and by which TMAO may influence atherosclerosis in humans require further clarification. The objective was to evaluate associations between the TMAO-DP and metabolomic profiles in postmenopausal women from the Women’s Health Initiative (WHI).

Prospective study of circulating metabolomic profiles and breast cancer incidence among predominantly premenopausal women.

Background: Associations between premenopausal plasma metabolites and breast cancer incidence are largely unknown.

Methods: We conducted a prospective, matched case-control study in which we measured pre-diagnostic metabolomic profiles among predominantly premenopausal women in the Nurses' Health Study II (n = 2010). Lipids, carbohydrates, and organic acid-related metabolites (n = 218) were profiled via liquid chromatography-tandem mass spectrometry.

Plasma and ovarian metabolomic responses to chronic stress in female mice.

Introduction: Chronic stress has been linked with higher risk of ovarian cancer and one posited pathway is through altered metabolism of amino acids, lipids, and other small molecule metabolites. However, the types of alterations that occur may not be uniform across tissue types.

Objectives: We aim to examine and compare the impacts of chronic stress on metabolomic changes in circulation and ovarian tissue.

Urinary Levels of Endocrine-Disrupting Chemicals and Breast Density in Young Women.

Background: Endocrine-disrupting chemicals (EDC) found in many household and personal care products have hormonal properties and effects on the mammary gland. It is unclear whether urinary concentrations of EDCs are associated with higher percent breast density, a major risk factor of breast cancer.

Methods: We conducted a cross-sectional study of 97 college-aged women.

Metabolomic evaluation of air pollution-related bone damage and potential mediation in Women's Health Initiative participants.

Ambient air pollution has been associated with bone damage. However, no studies have evaluated the metabolomic response to air pollutants and its potential influence on bone health in postmenopausal women. We analyzed data from Women's Health Initiative (WHI) participants with plasma samples.

Associations of Environmental Pollutant Mixtures and Red Blood Cell Folate Concentrations: A Mixture Analysis of the U.S. Adult Population Based on NHANES Data, 2007-2016.

Background: Folate is critical for many physiological processes, and low folate levels have been associated with a wide range of health outcomes, including chronic diseases and developmental outcomes. Many environmental chemicals are suspected to contribute to the etiology of health outcomes related to folate deficiency. However, little is known about how these pollutants influence folate levels as potential mechanistic pathways.

A multi-metabolite signature robustly predicts long-term mortality in the PREDIMED trial and several US cohorts.

Metabolome-based biomarkers contribute to identify mechanisms of disease and to a better understanding of overall mortality. In a long-term follow-up subsample (n = 1878) of the PREDIMED trial, among 337 candidate baseline plasma metabolites repeatedly assessed at baseline and after 1 year, 38 plasma metabolites were identified as predictors of all-cause mortality. Gamma-amino-butyric acid (GABA), homoarginine, serine, creatine, 1-methylnicotinamide and a set of sphingomyelins, plasmalogens, phosphatidylethanolamines and cholesterol esters were inversely associated with all-cause mortality, whereas plasma dimethylguanidino valeric acid (DMGV), choline, short and long-chain acylcarnitines, 4-acetamidobutanoate, pseudouridine, 7-methylguanine, N6-acetyllysine, phenylacetylglutamine and creatinine were associated with higher mortality.

Persistent PTSD symptoms are associated with plasma metabolic alterations relevant to long-term health: A metabolome-wide investigation in women.

Background: Post-traumatic stress disorder (PTSD) is characterized by severe distress and associated with cardiometabolic diseases. Studies in military and clinical populations suggest that dysregulated metabolomic processes may be a key mechanism. Prior work identified and validated a metabolite-based distress score (MDS) linked with depression and anxiety and subsequent cardiometabolic diseases.

Associations of Combined Genetic and Lifestyle Risks with Incident Type 2 Diabetes in the UK Biobank.

Background: Type 2 diabetes (T2D) results from a complex interplay between genetic predisposition and lifestyle factors. Both genetic susceptibility and unhealthy lifestyle are known to be associated with elevated T2D risk. However, their combined effects on T2D risk are not well studied.

Associations of cord blood concentrations of perfluoroalkyl substances with autistic traits in Singaporean children: The growing up in Singapore towards healthy outcomes study.

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive behaviors. Environmental pollutants may contribute to the etiology of ASD, but studies of perfluoroalkyl substances (PFAS) have shown conflicting results.

Objectives: We assessed associations between cord blood concentrations of PFAS with autistic traits at age seven years in a Singaporean birth cohort.

Metabolomic profiles of incident gallstone disease.

Background And Aims: Gallstone disease affects ≥40 million people in the USA and accounts for health costs of ≥$4 billion a year. Risk factors such as obesity and metabolic syndrome are well established. However, data are limited on relevant metabolomic alterations that could offer mechanistic and predictive insights into gallstone disease.

Differences in metabolomic profiles between Black and White women in the U.S.: Analyses from two prospective cohorts.

There is growing interest in incorporating metabolomics into public health practice. However, Black women are under-represented in many metabolomics studies. If metabolomic profiles differ between Black and White women, this under-representation may exacerbate existing Black-White health disparities.

Plasma metabolites of a healthy lifestyle in relation to mortality and longevity: Four prospective US cohort studies.

Background: A healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity.

A Plasma Metabolite Score Related to Psychological Distress and Diabetes Risk: A Nested Case-control Study in US Women.

Context: Psychological distress has been linked to diabetes risk. Few population-based, epidemiologic studies have investigated the potential molecular mechanisms (eg, metabolic dysregulation) underlying this association.

Objective: To evaluate the association between a metabolomic signature for psychological distress and diabetes risk.

Metabolomic profiles of chronic distress are associated with cardiovascular disease risk and inflammation-related risk factors.

Background: Chronic psychological distress is associated with increased risk of cardiovascular disease (CVD) and investigators have posited inflammatory factors may be centrally involved in these relationships. However, mechanistic evidence and molecular underpinnings of these processes remain unclear, and data are particularly sparse among women. This study examined if a metabolite profile linked with distress was associated with increased CVD risk and inflammation-related risk factors.

Metabolomic Evaluation of Air Pollution-related Bone Damage and Potential Mediation.

Ambient air pollution has been associated with bone damage. However, no studies have evaluated the metabolomic response to air pollutants and its potential influence on bone health in postmenopausal women. We analyzed data from WHI participants with plasma samples.

SpiderLearner: An ensemble approach to Gaussian graphical model estimation.

Gaussian graphical models (GGMs) are a popular form of network model in which nodes represent features in multivariate normal data and edges reflect conditional dependencies between these features. GGM estimation is an active area of research. Currently available tools for GGM estimation require investigators to make several choices regarding algorithms, scoring criteria, and tuning parameters.

Hyperinsulinemic and Pro-Inflammatory Dietary Patterns and Metabolomic Profiles Are Associated with Increased Risk of Total and Site-Specific Cancers among Postmenopausal Women.

We evaluated associations of the Empirical Dietary Index for Hyperinsulinemia (EDIH), Empirical Dietary Inflammatory Pattern (EDIP) and Healthy Eating Index (HEI2015) and their metabolomics profiles with the risk of total and site-specific cancers. We used baseline food frequency questionnaires to calculate dietary scores among 112,468 postmenopausal women in the Women's Health Initiative. We used multivariable-adjusted Cox regression to estimate hazard ratios (HR) and 95% confidence intervals for cancer risk estimation.

Association of Plasma Metabolomic Biomarkers With Persistent Tinnitus: A Population-Based Case-Control Study.

Importance: Persistent tinnitus is common, disabling, and difficult to treat.

Objective: To evaluate the association between circulating metabolites and persistent tinnitus.

Design, Setting, And Participants: This was a population-based case-control study of 6477 women who were participants in the Nurses' Health Study (NHS) and NHS II with metabolomic profiles and tinnitus data.

Psychological distress and metabolomic markers: A systematic review of posttraumatic stress disorder, anxiety, and subclinical distress.

Psychological distress can be conceptualized as an umbrella term encompassing symptoms of depression, anxiety, posttraumatic stress disorder (PTSD), or stress more generally. A systematic review of metabolomic markers associated with distress has the potential to reveal underlying molecular mechanisms linking distress to adverse health outcomes. The current systematic review extends prior reviews of clinical depressive disorders by synthesizing 39 existing studies that examined metabolomic markers for PTSD, anxiety disorders, and subclinical psychological distress in biological specimens.

Gaussian graphical models with applications to omics analyses.

Gaussian graphical models (GGMs) provide a framework for modeling conditional dependencies in multivariate data. In this tutorial, we provide an overview of GGM theory and a demonstration of various GGM tools in R. The mathematical foundations of GGMs are introduced with the goal of enabling the researcher to draw practical conclusions by interpreting model results.