Project description:BackgroundAlthough studies show that genomics and environmental stressors affect blood pressure, few studies have examined their combined effects, especially in African Americans.ObjectiveWe 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.MethodsThis 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.AnalysisThe 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.ImplicationsThe 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: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:BackgroundDepression is a risk factor for hypertension, yet few studies have been conducted in African American women.ObjectiveWe 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).MethodsLogistic 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).ResultsDepressive 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.ConclusionDepressive 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:IntroductionExperiencing psychosocial stress is associated with poor health outcomes such as hypertension and obesity, which are risk factors for developing cardiovascular disease. African American women experience disproportionate risk for cardiovascular disease including exposure to high levels of psychosocial stress. We hypothesized that psychosocial stress, such as perceived stress overload, may influence epigenetic marks, specifically DNA methylation (DNAm), that contribute to increased risk for cardiovascular disease in African American women.MethodsWe conducted an epigenome-wide study evaluating the relationship of psychosocial stress and DNAm among African American mothers from the Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) cohort. Linear mixed effects models were used to explore the epigenome-wide associations with the Stress Overload Scale (SOS), which examines self-reported past-week stress, event load and personal vulnerability.ResultsIn total, n = 228 participants were included in our analysis. After adjusting for known epigenetic confounders, we did not identify any DNAm sites associated with maternal report of stress measured by SOS after controlling for multiple comparisons. Several of the top differentially methylated CpG sites related to SOS score (P < 1 × 10-5), mapped to genes of unknown significance for hypertension or heart disease, namely, PXDNL and C22orf42.ConclusionsThis study provides foundational knowledge for future studies examining epigenetic associations with stress and other psychosocial measures in African Americans, a key area for growth in epigenetics. Future studies including larger sample sizes and replication data are warranted.
Project description:Trajectories and Influencing Factors of Psychological Distress in Nasopharyngeal Carcinoma Patients Receiving Radiotherapy (Incorporating Genetic Factors): A Multicenter Longitudinal Study
Project description:Background: This multicenter longitudinal study seeks to investigate the dynamic changes of psychological distress (PD) in nasopharyngeal carcinoma (NPC) patients during radiotherapy, and reveal the expression profiles and regulatory networks of circRNAs in these NPC patients. Methods: 282 newly diagnosed NPC patients from three hospitals in China were included. Participants completed questionnaires and provided blood samples. PD trajectories were identified via a latent class growth model (LCGM). Moreover, the factors that influence the PD trajectories were explored. Whole transcriptome sequencing was performed to investigate genetic factors. The real-time quantitative PCR was applied to validate circRNAs. We predicted the target mirnas, target Mrnas and target RNA-binding proteins (RBPs) of the top 10 malregulated circrnas. Subsequently, circRNA-miRNA-mRNA (ceRNA) and circRNA-RBP networks were constructed. In addition, the role of circRNA and target mRNA parent genes was predicted by KEGG and GO analysis. Results: LCGM identified two of the most important PD trajectories during radiotherapy in NPC patients: Class 1 “decline distress group” (11.0%) and Class 4 “rise distress group” (20.3%). Household monthly per capita income, coping strategies, and perceived social support emerged as important predictors of PD trajectories. Regarding genetic factors, 600 circRNAs and 123 miRNAs were identified as being significantly differentially expressed. Notably, hsa_circ_0004277 demonstrated significant differences between patients in the rise and decline distress groups (P < 0.01). ceRNA and RBP networks may influence the pathophysiology of PD in NPC patients undergoing radiotherapy. Conclusion: This study unraveled that PD trajectories in NPC patients during radiotherapy were heterogeneous, indicating the need for screening and timely interventions within this population. Furthermore, the expression patterns of ceRNA and circRNA–RBP networks and pathways related to these networks suggested a potential role of circRNAs in developing PD among NPC patients receiving radiotherapy.