Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations
Effects of Long-Term Averaging of Quantitative Blood Pressure Traits on the Detection of Genetic Associations
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DOI：
10.1016/j.ajhg.2014.06.002
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发表时间：
2014-07-13
影响因子：
9.8
通讯作者：
Chakravarti, Aravinda
中科院分区：
文献类型：
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作者：
Ganesh, Santhi K.;Chasman, Daniel I.;Chakravarti, Aravinda
血压（BP）是一种可遗传的数量性状，具有个体内变异性和对测量误差的敏感性。BP的遗传学研究通常使用单次访问测量，因此无法消除数月或数年内发生的变化。我们利用了这样的想法，即平均测量的血压随着时间的推移将提高表型的准确性，从而增加统计能力，以检测遗传关联。我们研究了46，629名欧洲血统个体的多年平均收缩压（SBP）、舒张压（DBP）、平均动脉压（MAP）和脉压（PP）。我们在19个独立的基因座上确定了39个性状变异关联（p < 5 × 10（-8））;五大协会在我们的LTA分析中唯一确定的四个位点中，包括2 p23的SBP和MAP（rs 1275988，KCNK 3附近），DBP在2q11.2（rs7599598，FER 1 L5中），PP在6p 21（rs 10948071，CRIP 3附近）和7 p13（rs 2949837，IGEBP 3附近）。在具有单次访视BP数据的队列中进行的复制分析显示，正相关复制和名义相关（p
Blood pressure (BP) is a heritable, quantitative trait with intraindividual variability and susceptibility to measurement error. Genetic studies of BP generally use single-visit measurements and thus cannot remove variability occurring over months or years. We leveraged the idea that averaging BP measured across time would improve phenotypic accuracy and thereby increase statistical power to detect genetic associations. We studied systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP) averaged over multiple years in 46,629 individuals of European ancestry. We identified 39 trait-variant associations across 19 independent loci (p < 5 x 10(-8)); five associations (in four loci) uniquely identified by our LTA analyses included those of SBP and MAP at 2p23 (rs1275988, near KCNK3), DBP at 2q11.2 (rs7599598, in FER1L5), and PP at 6p21 (rs10948071, near CRIP3) and 7p13 (rs2949837, near IGEBP3). Replication analyses conducted in cohorts with single-visit BP data showed positive replication of associations and a nominal association (p