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成人和儿童血压的全基因组分析。

Genome-wide profiling of blood pressure in adults and children.

机构信息

The Generation R Study Group (Ae-006), Erasmus Medical Center, PO Box 2040, 3000 CA Rotterdam, The Netherlands.

出版信息

Hypertension. 2012 Feb;59(2):241-7. doi: 10.1161/HYPERTENSIONAHA.111.179481. Epub 2011 Dec 27.

Abstract

Hypertension is an important determinant of cardiovascular morbidity and mortality and has a substantial heritability, which is likely of polygenic origin. The aim of this study was to assess to what extent multiple common genetic variants contribute to blood pressure regulation in both adults and children and to assess overlap in variants between different age groups, using genome-wide profiling. Single nucleotide polymorphism sets were defined based on a meta-analysis of genome-wide association studies on systolic blood pressure and diastolic blood pressure performed by the Cohort for Heart and Aging Research in Genome Epidemiology (n=29 136), using different P value thresholds for selecting single nucleotide polymorphisms. Subsequently, genetic risk scores for systolic blood pressure and diastolic blood pressure were calculated in an independent adult population (n=2072) and a child population (n=1034). The explained variance of the genetic risk scores was evaluated using linear regression models, including sex, age, and body mass index. Genetic risk scores, including also many nongenome-wide significant single nucleotide polymorphisms, explained more of the variance than scores based only on very significant single nucleotide polymorphisms in adults and children. Genetic risk scores significantly explained ≤1.2% (P=9.610(-8)) of the variance in adult systolic blood pressure and 0.8% (P=0.004) in children. For diastolic blood pressure, the variance explained was similar in adults and children (1.7% [P=8.910(-10)] and 1.4% [P=3.3*10(-5)], respectively). These findings suggest the presence of many genetic loci with small effects on blood pressure regulation both in adults and children, indicating also a (partly) common polygenic regulation of blood pressure throughout different periods of life.

摘要

高血压是心血管发病率和死亡率的重要决定因素,具有很大的遗传性,其遗传基础很可能是多基因的。本研究旨在评估多个常见遗传变异在多大程度上影响成人和儿童的血压调节,并使用全基因组分析评估不同年龄组之间变异的重叠情况。基于对收缩压和舒张压的全基因组关联研究的荟萃分析,使用不同的 P 值阈值来选择单核苷酸多态性,定义了单核苷酸多态性集。随后,在一个独立的成人人群(n=2072)和一个儿童人群(n=1034)中计算了收缩压和舒张压的遗传风险评分。使用线性回归模型评估遗传风险评分的解释方差,包括性别、年龄和体重指数。包括许多非全基因组显著单核苷酸多态性的遗传风险评分比仅基于成人和儿童非常显著单核苷酸多态性的评分解释了更多的方差。遗传风险评分显著解释了成人收缩压方差的≤1.2%(P=9.610(-8))和儿童收缩压方差的 0.8%(P=0.004)。对于舒张压,成人和儿童的解释方差相似(1.7%[P=8.910(-10)]和 1.4%[P=3.3*10(-5)])。这些发现表明,在成人和儿童中,血压调节存在许多遗传位点,这些遗传位点对血压的影响较小,这也表明在不同的生命阶段,血压的遗传调控具有(部分)共同的多基因调控。

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