Dataset Information

Using Genetic Burden Scores for Gene-by-Methylation Interaction Analysis on Metabolic Syndrome in African Americans.

ABSTRACT: With the rapid advancement of omics-based research, particularly big data such as genome- and epigenome-wide association studies that include extensive environmental and clinical variables, data analytics have become increasingly complex. Researchers face significant challenges regarding how to analyze multifactorial data and make use of the findings for clinical translation. The purpose of this article is to provide a scientific exemplar for use of genetic burden scores as a data analysis method for studies with both genotype and DNA methylation data in which the goal is to evaluate associations with chronic conditions such as metabolic syndrome (MetS). This study included 739 African American men and women from the Genetic Epidemiology Network of Arteriopathy Study who met diagnostic criteria for MetS and had available genetic and epigenetic data. Genetic burden scores for evaluated genes were not significant after multiple testing corrections, but DNA methylation at 2 CpG sites (dihydroorotate dehydrogenase cg22381196 pFDR = .014; CTNNA3 cg00132141 pFDR = .043) was significantly associated with MetS after controlling for multiple comparisons. Interactions between the marginally significant CpG sites and burden scores, however, were not significant. More work is required in this area to identify intermediate biological pathways influenced by environmental, genetic, and epigenetic variation that may explain the high prevalence of MetS among African Americans. This study does serve, however, as an example of the use of the genetic burden score as an alternative data analysis approach for complex studies involving the analysis of genetic and epigenetic data simultaneously.

SUBMITTER: Taylor JY

PROVIDER: S-EPMC6700897 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Using Genetic Burden Scores for Gene-by-Methylation Interaction Analysis on Metabolic Syndrome in African Americans.

Taylor Jacquelyn Y JY Ware Erin B EB Wright Michelle L ML Smith Jennifer A JA Kardia Sharon L R SLR

Biological research for nursing 20190219 3

With the rapid advancement of omics-based research, particularly big data such as genome- and epigenome-wide association studies that include extensive environmental and clinical variables, data analytics have become increasingly complex. Researchers face significant challenges regarding how to analyze multifactorial data and make use of the findings for clinical translation. The purpose of this article is to provide a scientific exemplar for use of genetic burden scores as a data analysis metho ...[more]

PMID: 30781968

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Project description:BackgroundBinary definitions of the metabolic syndrome based on the presence of a particular number of individual risk factors are limited, particularly in the pediatric population. To address this limitation, we aimed at constructing composite and continuous metabolic syndrome scores (cmetS) to represent an overall measure of metabolic syndrome (MetS) in a large cohort of metabolically at-risk children, focusing on the use of the usual clinical parameters (waist circumference (WC) and systolic blood pressure (SBP), supplemented with two salivary surrogate variables (glucose and high density lipoprotein cholesterol (HDLC). Two different approaches used to create the scores were evaluated in comparison.MethodsData from 8,112 Kuwaiti children (10.00 ± 0.67 years) were used to construct two cmetS for each subject. The first cmetS (cmetS-Z) was created by summing standardized residuals of each variable regressed on age and gender; and the second cmetS (cmetS-PCA) was defined as the first principal component from gender-specific principal component analysis based on the four variables.ResultsThere was a graded relationship between both scores and the number of adverse risk factors. The areas under the curve using cmetS-Z and cmetS-PCA as predictors for severe metabolic syndrome (defined as the presence of ≥3 metabolic risk factors) were 0.935 and 0.912, respectively. cmetS-Z was positively associated with WC, SBP, and glucose, but inversely associated with HDLC. Except for the lack of association with glucose, cmetS-PCA was similar to cmetS-Z in boys, but had minimum loading on HDLC in girls. Analysis using quantile regression showed an inverse association of fitness level with cmetS-PCA (p = 0.001 for boys; p = 0.002 for girls), and comparison of cmetS-Z and cmetS-PCA suggested that WC and SBP were main contributory components. Significant alterations in the relationship between cmetS and salivary adipocytokines were demonstrated in overweight and obese children as compared to underweight and normal-weight children.ConclusionWe have derived continuous summary scores for MetS from a large-scale pediatric study using two different approaches, incorporating salivary measures as surrogate for plasma measures. The derived scores were viable expressions of metabolic risk, and can be utilized to study the relationships of MetS with various aspects of the metabolic disease process.

Project description:BackgroundTargeting habit-development (behavioral automaticity) as part of healthy lifestyle behavior change interventions may improve the adoption and maintenance of healthful behaviors. Few studies, however, have evaluated the feasibility of using a habit-development approach to foster the adoption of recommended physical activity and dietary behaviors. We report quantitative and qualitative data from a feasibility study evaluating a habit-formation intervention to foster healthy dietary and physical activity habits among middle aged African Americans with metabolic syndrome.MethodsUsing a non-comparative design we evaluated the feasibility an 8-week, hybrid format (telecoaching and face-to-face sessions), habit-focused intervention targeting the development of healthful dietary and physical activity habit development among 24 African Americans aged 40 and older with metabolic syndrome recruited from the emergency department - a setting where individuals in under-resourced communities often go for primary care. We administered behavioral automaticity measures tailored to participants' self-selected habits biweekly during the intervention and collected clinical outcomes of systolic blood pressure, weight, waist circumference, and BMI at baseline week 20.ResultsParticipant attrition from the program was high (~ 50%). Despite high levels of attrition, 92% of intervention completers were extremely satisfied with the program. Intervention completers also experienced gains in behavioral automaticity for both dietary and physical activity habits. Overall, higher levels of adherence were associated with higher positive gains in automaticity with the statistical significance of the associations being more pronounced for physical activity habit plans relative to dietary habit plans.ConclusionsOur preliminary data support a habit-development approach for fostering the adoption of healthful dietary and physical activity habits. However, in this pilot study high rates of attrition were seen, suggesting that strategies to improve retention and participant engagement should be included in future studies, particularly when targeting African American emergency department patients.Trial registrationClinicalTrials.gov ID: NCT03370419 Registered 12/11/2017, retrospectively registered.

Dataset Information

Using Genetic Burden Scores for Gene-by-Methylation Interaction Analysis on Metabolic Syndrome in African Americans.

Publications

Using Genetic Burden Scores for Gene-by-Methylation Interaction Analysis on Metabolic Syndrome in African Americans.

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