Project description:BACKGROUND:Although studies show that genomics and environmental stressors affect blood pressure, few studies have examined their combined effects, especially in African Americans. OBJECTIVE:We present the recruitment methods and psychological measures of the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) study, which seeks to investigate the individual and combined effects of genetic (G) and environmental (E) (psychological) stressors on blood pressure in African American mother-child dyads. Genetic methods are presented elsewhere, but here we present the recruitment methods, psychological measures, and analysis plan for these environmental stressors. METHODS:This longitudinal study will enroll 250 mother-child dyads (N = 500). Study participation is restricted to women who (a) are ?21 years of age, (b) self-identify as African American or Black, (c) speak English, (d) do not have an identified mental illness or cognitive impairment, and (e) have a biological child between 3 and 5 years old. The primary environmental stressors assessed are parenting stress, perceived racism and discrimination, and maternal mental health. Covariates include age, cigarette smoking (for mothers), and gender (for children). The study outcome variables are systolic and diastolic blood pressure. ANALYSIS:The main analytic outcome is genetic-by-environment interaction analyses (G × E); however, main effects (G) and (E) will be individually assessed first. Genetic (G) and interaction analyses (G × E) are described in a companion paper and will include laboratory procedures. Statistical modeling of environmental stressors on blood pressure will be done using descriptive statistics and generalized estimating equation models. IMPLICATIONS:The methodology presented here includes the study rationale, community engagement and recruitment protocol, psychological variable measurement, and analysis plan for assessing the association of environmental stressors and blood pressure. This study may provide the foundation for other studies and development of interventions to reduce the risk for hypertension and to propose targeted health promotion programs for this high-risk population.
Project description:Depression is a risk factor for hypertension, yet few studies have been conducted in African American women. We conducted a secondary analysis of depressive symptoms and high blood pressure among African American women from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure longitudinal study (N = 250). Logistic regression was used to examine depressive symptoms and blood pressure, adjusting for education, employment, and racism/discrimination. Growth curve modeling was used to investigate longitudinal associations between depressive symptoms and systolic (SBP) and diastolic (DBP) blood pressures at 4 time points (T1-T4). Depressive symptoms at baseline were not prospectively associated with hypertension prevalence. Participants with Beck Depression Inventory scores higher than 10 had higher estimated marginal SBP and DBP over time compared with participants with lower scores. Depressive symptoms were not associated with hypertension prevalence at T4, but they were associated with higher estimated marginal SBP and DBP. Future research is needed to elucidate mechanisms and implications for clinical care and prevention.
Project description:The Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) study aims to delineate the independent and interaction effects of genomic (genetic and epigenetic) and psychological-environmental (maternally perceived racial discrimination, mental health, and parenting behavior) factors on blood pressure (BP) among African American mother-child dyads over time. The purpose of this article is to describe the two-step genetic and epigenetic approach that will be executed to explore Gene × Environment interactions on BP using a longitudinal cohort design. Procedure for the single collection of DNA at Time 1 includes the use of the Oragene 500-format saliva sample collection tube, which provides enough DNA for both the Illumina Multi-Ethnic Genotyping and 850K EPIC methylation analyses. BP readings, height, weight, percentage of body fat, and percentage of body water will be measured on all participants every 6 months for 2 years for a total of 4 time points. Genomic data analyses to be completed include multivariate modeling, assessment of population admixture and structure, and extended analyses including Bonferroni correction, false discovery rate methods, Monte Carlo approach, EIGENSTRAT methods, and so on, to determine relationships among both main and interaction effects of genetic, epigenetic, and psychological environmental factors on BP.
Project description:Blood plasma was collected from 9 naval aviation students 24 hours prior to and no more than 20 minutes after Modular Egress Training (psychological stressor).
Project description:Genome-wide association studies (GWAS) have identified blood pressure-related loci, but functional insights into causality and related molecular mechanisms lag behind. We functionally characterize 4608 genetic variants in linkage with blood pressure loci in vascular smooth muscle cells (VSMCs) and cardiomyocytes (CMs) by massively parallel reporter assays (MPRAs). Regulatory variants are in non-conserved loci, enriched in repeats, and alter trait-relevant transcription factor binding sites. Higher-order genome organization indicates that loci harboring regulatory variants converge in spatial hubs to control specific signaling pathways required for proper cardiovascular function. Modelling different variant allele frequencies by CRISPR prime editing led to expression changes of KCNK9, SFXN2, and PCGF6. We provide mechanistic insights into how regulatory variants converge their effects on blood pressure genes (i.e. ULK4, MAP4, CFDP1, PDE5A, 10q24.32), and cardiovascular pathways. Our findings support advances in molecular precision medicine to define functionally relevant variants and the genetic architecture of blood pressure genes.
Project description:Individual differences in basal leukocyte gene expression profiles as a function of hedonic and eudaimonic well-being, and psychological and social sub-dimensions of eudaimonic well-being. Gene expression profiling was carried out on peripheral blood mononuclear cell RNA samples collected from 122 healthy adults measured for hedonic and eudaimonic dimensions of well-being using the Short Flourishing Scale (Keyes, C (2014). The Mental Health Continuum-Short Form (MHC-SF) for adults). Higher values of the hedonic well-being scale indicate greater levels of positive affect, higher values of eudaimonic well-being scale indicate greater experience of purpose and meaning in life, higher values of social well-being scale indicate greater experience of social well-being in life, higher values of psychological well-being scale indicate greater experience of psychological well-being in life, greater TotalMHCSF scores indicate greater experience of all forms of well-being measured by the MHC-SF, the FlourishGroup indicates idividuals showing flourishing mental health as defined by the MHC-SF scoring instructions referenced above, greater BrownPsychological scores indicate greater experience of psychological well-being as measured by the MHC-SF with an alternative scoring, and greater BrownSocial scores indicate greater experience of social well-being as measured by the MHC-SF with an alternative scoring.