Direct Estimates of the Genomic Contributions to Blood Pressure Heritability within a Population-Based Cohort (ARIC).
Direct Estimates of the Genomic Contributions to Blood Pressure Heritability within a Population-Based Cohort (ARIC).
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DOI：
10.1371/journal.pone.0133031
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Chakravarti A
中科院分区：
文献类型：
--
作者：
Salfati E;Morrison AC;Boerwinkle E;Chakravarti A
血压（BP）是一种遗传性状，受多种环境和遗传因素的影响，目前来自双胞胎和家庭研究的遗传率估计约为40%。在这里，我们使用来自社区动脉粥样硬化风险（ARIC）研究的全基因组多态性数据来估计队列成员之间基因组相关性的BP遗传力。我们分别利用8,901名欧洲血统（EA）和2,860名非洲血统（AA） ARIC参与者的6,365,596和9,578,528个基因分型和估算的常见单核苷酸多态性（snp）数据，并使用混合线性模型进行分析，得出了四个观察结果。首先，对于血压测量，欧洲和非洲血统个体的收缩压(SBP)/舒张压（DBP）的遗传率分别为~20%/~50%和~27%/~39%，与先前的研究一致。其次，在这些数据中，等位基因频率为bbb10 %的常见变异再现了大部分BP遗传力。第三，绝大多数BP遗传力因染色体而异，取决于其长度，并且主要集中在标记为DNaseI超敏感位点（DHSs）的非编码基因组区域。第四，这种遗传性大部分来自目前已知的不含心血管和肾脏基因的位点。最近对大规模全基因组关联研究（GWASs）和混合定位的荟萃分析发现了约50个与BP和高血压（HTN）相关的位点，但它们只占遗传力的一小部分（约2%）。
Blood pressure (BP) is a heritable trait with multiple environmental and genetic contributions, with current heritability estimates from twin and family studies being ~ 40%. Here, we use genome-wide polymorphism data from the Atherosclerosis Risk in Communities (ARIC) study to estimate BP heritability from genomic relatedness among cohort members. We utilized data on 6,365,596 and 9,578,528 genotyped and imputed common single nucleotide polymorphisms (SNPs), in 8,901 European ancestry (EA) and 2,860 African Ancestry (AA) ARIC participants, respectively, and a mixed linear model for analyses, to make four observations. First, for BP measurements, the heritability is ~20%/~50% and ~27%/~39% for systolic (SBP)/diastolic (DBP) blood pressure in European and African ancestry individuals, respectively, consistent with prior studies. Second, common variants with allele frequency >10% recapitulate most of the BP heritability in these data. Third, the vast majority of BP heritability varies by chromosome, depending on its length, and is largely concentrated in noncoding genomic regions annotated as DNaseI hypersensitive sites (DHSs). Fourth, the majority of this heritability arises from loci not harboring currently known cardiovascular and renal genes. Recent meta-analyses of large-scale genome-wide association studies (GWASs) and admixture mapping have identified ~50 loci associated with BP and hypertension (HTN), and yet they account for only a small fraction (~2%) of the heritability.