Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
Sci Rep. 2021 Feb 18;11(1):4075. doi: 10.1038/s41598-021-83450-3.
Genome-wide association studies (GWAS) have identified thousands of genetic loci associated with cross-sectional blood pressure (BP) traits; however, GWAS based on longitudinal BP have been underexplored. We performed ethnic-specific and trans-ethnic GWAS meta-analysis using longitudinal and cross-sectional BP data of 33,720 individuals from five cohorts in the US and one in Brazil. In addition to identifying several known loci, we identified thirteen novel loci with nine based on longitudinal and four on cross-sectional BP traits. Most of the novel loci were ethnic- or study-specific, with the majority identified in African Americans (AA). Four of these discoveries showed additional evidence of association in independent datasets, including an intergenic variant (rs4060030, p = 7.3 × 10) with reported regulatory function. We observed a high correlation between the meta-analysis results for baseline and longitudinal average BP (rho = 0.48). BP trajectory results were more correlated with those of average BP (rho = 0.35) than baseline BP(rho = 0.18). Heritability estimates trended higher for longitudinal traits than for cross-sectional traits, providing evidence for different genetic architectures. Furthermore, the longitudinal data identified up to 20% more BP known associations than did cross-sectional data. Our analyses of longitudinal BP data in diverse ethnic groups identified novel BP loci associated with BP trajectory, indicating a need for further longitudinal GWAS on BP and other age-related traits.
全基因组关联研究(GWAS)已经确定了数千个与横断面血压(BP)特征相关的遗传位点;然而,基于纵向 BP 的 GWAS 研究仍未得到充分探索。我们使用来自美国五个队列和巴西一个队列的 33720 名个体的纵向和横断面 BP 数据进行了基于种族的和跨种族的 GWAS 荟萃分析。除了确定了几个已知的位点外,我们还确定了 13 个新的与 9 个纵向和 4 个横断面 BP 特征相关的位点。大多数新的位点是种族特异性或研究特异性的,其中大多数是在非裔美国人(AA)中发现的。其中四个发现的结果在独立数据集中有进一步的关联证据,包括一个位于基因间的变异体(rs4060030,p=7.3×10),具有报道的调节功能。我们观察到基线和纵向平均 BP 的荟萃分析结果之间存在高度相关性(rho=0.48)。BP 轨迹的结果与平均 BP(rho=0.35)比基线 BP(rho=0.18)更相关。纵向特征的遗传度估计趋势高于横断面特征,为不同的遗传结构提供了证据。此外,纵向数据比横断面数据识别出多达 20%的已知 BP 关联。我们对不同种族群体的纵向 BP 数据的分析确定了与 BP 轨迹相关的新的 BP 位点,表明需要对 BP 和其他与年龄相关的特征进行进一步的纵向 GWAS。