Bonati Maria Teresa, Graziano Francesca, Monti Maria Cristina, Crocamo Cristina, Terradura-Vagnarelli Oscar, Cirillo Massimo, Lanti Mariapaola, Laurenzi Martino, Mancini Mario, Menotti Alessandro, Grassi Mario, Zanchetti Alberto
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.
J Hypertens. 2014 Nov;32(11):2179-87. doi: 10.1097/HJH.0000000000000311.
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.
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.
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.
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.
对人群心血管危险因素进行前瞻性研究,为剖析诸如动脉血压(BP)这类随时间变化的定量复杂性状的多基因和环境成分提供了独特契机。在古比奥人群研究中,对711个核心家系的2620名患者进行了BP遗传力分析,这些患者在25年期间可进行随访。
通过潜在曲线模型预测每位患者的BP系列测量值,将其总结为个体截距(基线预期值)和斜率(与时间相关的变化)。这些模型将年龄(以年计)或波次(首次调查后的时间)作为时间轴,并在遗传力分析中使用针对性别、年龄和临床变量进行调整的加性多基因 - 共同环境 - 独特误差模型在家庭层面进行关联。
加性遗传效应解释了基线时收缩压(SBP)值方差的32% - 49%,采用核心家系和同胞 - 家庭矩阵进行的波次依赖性分析得出的遗传力值更高。在按年龄进行的分析中,舒张压(DBP)基线值的遗传力低于收缩压(5% - 15%),但在按波次进行的分析中,其遗传力范围与收缩压相同(36% - 37%)。在按年龄进行的分析中,加性遗传效应解释的血压随时间变化(斜率)分别为收缩压的33%至43%和舒张压的24%至25%。共同环境也产生了显著影响,但对这两个性状方差的解释比例较小(4% - 17%)。
来自古比奥人群的纵向数据显示,遗传因素对收缩压和舒张压基线值以及随时间变化有强到中等程度的影响,环境因素的影响较小但显著。