Heritability and Genetic Linkage of Plasma Natriuretic Peptide Levels

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Abstract
Background— Natriuretic peptides play a critical role in the maintenance of salt and water homeostasis and regulation of vascular tone. Thus, interindividual variation in plasma natriuretic peptide levels may contribute to variation in susceptibility to volume overload and hypertension. It is unknown to what extent genetic factors contribute to variation in plasma natriuretic peptide levels. Methods and Results— We studied 1914 Framingham Study participants (mean age 57 years, 53% women) who underwent routine echocardiography and testing for plasma N-terminal proatrial natriuretic peptide (N-ANP) and brain natriuretic peptide (BNP). We estimated sex-specific multivariable models and used variance-components methods, implemented in SOLAR (Sequential Oligogenic Linkage Analysis Routines), to estimate heritability. Multipoint linkage analyses were performed using data from a 10-cM-density genome scan. Age, clinical, and echocardiographic variables accounted for 42% and 40% of the variation in log N-ANP and log BNP levels, respectively, in men. Corresponding values in women were 27% and 21%. Multivariable-adjusted heritabilities were 0.44 for log N-ANP and 0.35 for log BNP ( P Conclusions— In this community-based sample, a substantial proportion of the unexplained variation in plasma natriuretic peptide levels was attributable to additive genetic effects. Additional studies using candidate gene approaches may provide insight into the genetic loci that regulate plasma natriuretic peptide levels in humans.