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The Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) Study: Design and Methods for Complex DNA Analysis.

ABSTRACT: 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.

SUBMITTER: Taylor JY

PROVIDER: S-EPMC5025343 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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:Minimal clinical research has investigated the significance of different blood pressure monitoring techniques in the ICU and whether systolic vs. mean blood pressures should be targeted in therapeutic protocols and in defining clinical study cohorts. The objectives of this study are to compare real-world invasive arterial blood pressure with noninvasive blood pressure, and to determine if differences between the two techniques have clinical implications.We conducted a retrospective study comparing invasive arterial blood pressure and noninvasive blood pressure measurements using a large ICU database. We performed pairwise comparison between concurrent measures of invasive arterial blood pressure and noninvasive blood pressure. We studied the association of systolic and mean invasive arterial blood pressure and noninvasive blood pressure with acute kidney injury, and with ICU mortality.Adult intensive care units at a tertiary care hospital.Adult patients admitted to intensive care units between 2001 and 2007.None.Pairwise analysis of 27,022 simultaneously measured invasive arterial blood pressure/noninvasive blood pressure pairs indicated that noninvasive blood pressure overestimated systolic invasive arterial blood pressure during hypotension. Analysis of acute kidney injury and ICU mortality involved 1,633 and 4,957 patients, respectively. Our results indicated that hypotensive systolic noninvasive blood pressure readings were associated with a higher acute kidney injury prevalence (p = 0.008) and ICU mortality (p < 0.001) than systolic invasive arterial blood pressure in the same range (?70 mm Hg). Noninvasive blood pressure and invasive arterial blood pressure mean arterial pressures showed better agreement; acute kidney injury prevalence (p = 0.28) and ICU mortality (p = 0.76) associated with hypotensive mean arterial pressure readings (?60 mm Hg) were independent of measurement technique.Clinically significant discrepancies exist between invasive and noninvasive systolic blood pressure measurements during hypotension. Mean blood pressure from both techniques may be interpreted in a consistent manner in assessing patients' prognosis. Our results suggest that mean rather than systolic blood pressure is the preferred metric in the ICU to guide therapy.

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The Intergenerational Impact of Genetic and Psychological Factors on Blood Pressure (InterGEN) Study: Design and Methods for Complex DNA Analysis.

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