Body mass index modulates blood pressure heritability: the Family Blood Pressure Program.

High blood pressure (BP) contributes to 12.8% (or 7.5 million) of deaths worldwide.1 Although BP traits have a substantial genetic component (heritability estimates ranging 31%–68%),2 only a small fraction of the BP variation has been explained by significant single nucleotide polymorphisms identified through genome-wide association studies.3–11 The high prevalence of obesity (44.1% of black, 32.8% of White, and 37.9% of Hispanic American adults are obese (body mass index (BMI) ≥ 30kg/m2)),12 coupled with reports of significant interactions between genes and BMI from candidate gene and twin studies of BP,13–20 has inspired large-scale systematic investigations of gene–obesity interactions. However, meta-analyses of genome-wide association study results using massive sample sizes have yet to identify any genome-wide significant (P ≤ 5×10−8) single nucleotide polymorphism–BMI interactions. We investigated whether large and racially diverse family studies provided any evidence for gene–BMI interactions in hypertension pathophysiology and whether the shape (unimodal, linear increasing, linear decreasing) of this interaction was race dependent. Specifically, we investigated the BP heritability dependence on BMI using 4,153 black, 1,538 Asian, 4,013 White, and 2,199 Hispanic American participants from the Family Blood Pressure Program (FBPP). Within each of 10 race and network subgroups, we employed the Shi and Rao21 generalized variance components model to allow the polygenic component, and hence BP heritability, to vary by BMI level. We modeled 2 polygenic–BMI interaction functions (linear and Gaussian) to permit a variety of heritability curve shapes (increasing, decreasing, unimodal) for each of 4 BP traits (systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP)). The resulting heritability curves may provide insight into the genetic and environmental architecture of BP and is an important first step in exploring the existence and shape of gene–BMI interactions.