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(Circulation. 2003;108:13.)
© 2003 American Heart Association, Inc.

Brief Rapid Communication

Heritability and Genetic Linkage of Plasma Natriuretic Peptide Levels

Thomas J. Wang, MD; Martin G. Larson, ScD; Daniel Levy, MD; Emelia J. Benjamin, MD, ScM; Diane Corey, BS; Eric P. Leip, MS; Ramachandran S. Vasan, MD

From the Framingham Heart Study, Framingham, Mass (T.J.W., M.G.L., D.L., E.J.B., D.C., E.P.L., R.S.V.); Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Mass (T.J.W.); National Heart, Lung, and Blood Institute, Bethesda, Md (D.L.); and Cardiology Section, Boston University School of Medicine, Boston, Mass (D.L., E.J.B., R.S.V.).

Correspondence to Ramachandran Vasan, MD, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702-5827. E-mail vasan{at}fram.nhlbi.nih.gov

Received January 21, 2003; de novo received April 16, 2003; revision received May 16, 2003; accepted May 21, 2003.

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<0.0001). Genome-wide linkage analyses, based on 1142 participants from the 314 largest families, revealed 2 regions of suggestive linkage for log N-ANP and log BNP on chromosomes 2p25 (log-of-odds score 2.40) and 12p13 (log-of-odds score 2.13), respectively.

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.

Key Words: natriuretic peptides • genetics • epidemiology • atrial natriuretic factor

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