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Heritability of blood pressure through latent curve trajectories in families from the Gubbio population study

Bonati, Maria Teresaa; Graziano, Francescaa,b; Monti, Maria Cristinaa,c; Crocamo, Cristinaa,c; Terradura-Vagnarelli, Oscard; Cirillo, Massimoe; Lanti, Mariapaolaf; Laurenzi, Martinod; Mancini, Mariog; Menotti, Alessandrof; Grassi, Mariob; Zanchetti, Albertoa,h

doi: 10.1097/HJH.0000000000000311
ORIGINAL PAPERS: Genetics/epigenetics

Background and objectives: Prospective investigations on cardiovascular risk factors in populations provide a unique opportunity to dissect time-dependent quantitative complex traits, such as arterial blood pressure (BP), into their polygenic and environmental components. BP heritability analyses were carried out on 2620 patients belonging to 711 nuclear pedigrees that could be followed up throughout 25 years in the Gubbio Population Study.

Methods: Each patient's BP serial measurements were summarized into individual intercepts (expected values at baseline) and slopes (time-related changes), which were predicted through latent curve models. These models considered either age in years or waves (times from the first survey) as time axis and were linked at a family level in the heritability analyses using additive polygenic–common environment–unique error models adjusted for sex, age and clinical variables.

Results: The additive genetic effect explained 32–49% of the variance of SBP values at baseline, the wave-dependent analysis with nuclear pedigrees and the sibs-household matrix accounting for higher heritability values. Heritability of DBP baseline value was lower than that of SBP in analyses by age (5–15%), but fell in the same heritability range as SBP on the analysis by waves (36–37%). The BP variation over time (slope) explained by an additive genetic effect ranged from 33 to 43% and from 24 to 25% for SBP and DBP, respectively, in the analysis by age. Shared environment also exerted a significant influence, but explained a smaller portion of the variances (4–17%) for both traits.

Conclusion: Longitudinal data from the Gubbio population show strong to moderate genetic influences on SBP and DBP baseline values and changes over time with a smaller, though significant, effect of environment.

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aIstituto Auxologico Italiano, IRCCS, Milan

bDipartimento di Scienze del Sistema Nervoso e del Comportamento, Università di Pavia

cDipartimento di Sanità Pubblica, Medicina Sperimentale e Forense, Università di Pavia

dCentro di Medicina Preventiva, Gubbio

eDipartimento di Medicina e Chirurgia, Università di Salerno

fAssociation for Cardiac Research, Rome

gDipartimento di Medicina Clinica e Sperimentale, Università Federico II, Napoli

hUniversità di Milano, Centro di Fisiologia Clinica e Ipertensione, Italy

Correspondence to Professor Alberto Zanchetti, Istituto Auxologico Italiano, Via L. Ariosto 13, 20145, Milan, Italy. Tel: +39 02 619112237; fax: +39 02 619112901; e-mail:

Abbreviations: ACE, additive polygenic–common environment–unique error; BP, blood pressure; C2, household or sibs-household effect according to the analysis, by using extended or nuclear pedigrees, respectively; FIMLEs, ‘Full Information’ Maximum Likelihood Estimates; H2, heritability; HDL, high-density lipoprotein; I, intercept; LCM, latent curve model; MAR, missing at random; MLE, maximum likelihood estimate; Q, curvature; RMSEA, root-mean-square error of approximation; S, slope; SE, standard error; SOLAR, Sequential Oligogenic Linkage Analysis Routine

Received 3 December, 2013

Revised 18 June, 2014

Accepted 18 June, 2014

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