Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
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许多遗传位点影响欧洲人的收缩压（SBP）和舒张压（DBP）。我们现在报告全基因组范围内的脉压（PP）和平均动脉压（MAP）的关联研究。在发现（N= 74，064）和随访研究（N= 48，607），我们在全基因组显著性上鉴定了（P= 2.7×10-8 ~ P=2.3×10-13）4个新的PP位点（4 q12靠近CHIC 2/PDGFRAI，7q22.3靠近PIK 3CG，8q24.12在NOV，11q24.3靠近ADAMTS-8），两个新的MAP基因座，（MAP 4中的3p21.31，ADRB 1附近的10q25.3）和一个与这两个性状相关的基因座（FIGN附近的2q24.3），该基因座最近与东亚人的SBP相关。对于三种新的PP信号，SBP的估计效应与DBP的估计效应相反，与大多数常见的SBP和DBP相关变异体相反，这些变异体对两种性状均显示出一致的效应。这些发现表明了血压变化的新遗传机制，包括可能差异影响SBP和DBP的途径。
Numerous genetic loci influence systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans . We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N=74,064) and follow-up studies (N=48,607), we identified at genome-wide significance (P= 2.7×10-8 to P=2.3×10-13) four novel PP loci (at 4q12 near CHIC2/PDGFRAI, 7q22.3 near PIK3CG, 8q24.12 in NOV, 11q24.3 near ADAMTS-8), two novel MAP loci (3p21.31 in MAP4, 10q25.3 near ADRB1) and one locus associated with both traits (2q24.3 near FIGN) which has recently been associated with SBP in east Asians. For three of the novel PP signals, the estimated effect for SBP was opposite to that for DBP, in contrast to the majority of common SBP- and DBP-associated variants which show concordant effects on both traits. These findings indicate novel genetic mechanisms underlying blood pressure variation, including pathways that may differentially influence SBP and DBP.