Aggregate blood pressure responses to serial dietary sodium and potassium intervention: defining responses using independent component analysis

Gengsheng Chen, Lisa de las Fuentes, Chi C. Gu, Jiang He, Dongfeng Gu, Tanika Kelly, James Hixson, Cashell Jacquish, D. C. Rao, Treva K. Rice

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. In 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 %). In summary, the present study provides intermediate phenotypes that are heritable. Using these derived components may prove useful in gene discovery applications.