Body Mass Index Modulates Blood Pressure Heritability: The Family Blood Pressure Program

BACKGROUND: Candidate gene and twin studies suggest that interactions between body mass index (BMI) and genes contribute to the variability of blood pressure (BP). To determine whether there is evidence for gene-BMI interactions, we investigated the modulation of BP heritability by BMI using 4,153 blacks, 1,538 Asians, 4,013 whites, and 2,199 Hispanic Americans from the Family Blood Pressure Program. METHODS: To capture the BP heritability dependence on BMI, we employed a generalized variance components model incorporating linear and Gaussian interactions between BMI and the genetic component. Within each race and network subgroup, we used the Akaike information criterion and likelihood ratio test to select the appropriate interaction function for each BP trait (systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)) and determine interaction significance, respectively. RESULTS: BP heritabilities were significantly modified by BMI in the GenNet and SAPPHIRe Networks, which contained the youngest and least-obese participants, respectively. GenNet Whites had unimodal SBP, MAP, and PP heritabilities that peaked between BMI values of 33 and 37kg/m(2). The SBP and MAP heritabilities in GenNet Hispanic Americans, as well as the PP heritability in GenNet blacks, were increasing functions of BMI. The DBP and SBP heritabilities in the SAPPHIRe Chinese and Japanese, respectively, were decreasing functions of BMI. CONCLUSIONS: BP heritability differed by BMI in the youngest and least-obese networks, although the shape of this dependence differed by race. Use of nonlinear gene-BMI interactions may enhance BP gene discovery efforts in individuals of European ancestry.