Abstract
BackgroundHypertension is a complex trait that often co-occurs with other conditions such as obesity and is affected by genetic and environmental factors. Aggregate indices such as principal components among these variables and their responses to environmental interventions may represent novel information that is potentially useful for genetic studies.ResultsIn this study of families participating in the Genetic Epidemiology Network of Salt Sensitivity (GenSalt) Study, blood pressure (BP) responses to dietary sodium interventions are explored. Independent component analysis (ICA) was applied to 20 variables indexing obesity and BP measured at baseline and during low sodium, high sodium and high sodium plus potassium dietary intervention periods. A “heat map” protocol that classifies subjects based on risk for hypertension is used to interpret the extracted components. ICA and heat map suggest four components best describe the data: (1) systolic hypertension, (2) general hypertension, (3) response to sodium intervention and (4) obesity. The largest heritabilities are for the systolic (64 %) and general hypertension (56 %) components. There is a pattern of higher heritability for the component response to intervention (40–42 %) as compared to those for the traditional intervention responses computed as delta scores (24 %–40 %).ConclusionsIn summary, the present study provides intermediate phenotypes that are heritable. Using these derived components may prove useful in gene discovery applications.Electronic supplementary materialThe online version of this article (doi:10.1186/s12863-015-0226-8) contains supplementary material, which is available to authorized users.
Highlights
Hypertension is a complex trait that often co-occurs with other conditions such as obesity and is affected by genetic and environmental factors
Hypertension is a major risk factor for many cardiovascular diseases. [1, 2] there is evidence for substantial heritability as well as environmental causes underlying these diseases. [3,4,5] For example, an environmental intervention of reduced sodium and/or increased potassium intake can lead to reduced systolic and diastolic blood pressure (BP) [6,7,8,9,10,11], and familial factors in part underlie these BP responses to sodium intervention. [11,12,13,14,15,16] significant inter-correlations among this set of variables suggest a complex underlying network involving multiple genes
Study subjects The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) study was designed to identify genes related to variation in BP responses to dietary sodium [24]
Summary
Hypertension is a complex trait that often co-occurs with other conditions such as obesity and is affected by genetic and environmental factors. Aggregate indices such as principal components among these variables and their responses to environmental interventions may represent novel information that is potentially useful for genetic studies. [11,12,13,14,15,16] significant inter-correlations among this set of variables suggest a complex underlying network involving multiple genes, Traditionally, principal component analysis (PCA) [20] is used to identify uncorrelated factors. The purpose of this report is to construct endophenotypes using ICA analysis of several obesity and BP measures during a sodium intervention test in the GenSalt study, and assess their utility using heritability analysis. The utilities of the endophenotypes for future genetic applications were evaluated by heritability analysis
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