Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk
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DOI：
10.1038/ng.3768
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发表时间：
2017-03-01
期刊：
影响因子：
30.8
通讯作者：
Ehret, Georg B.
中科院分区：
文献类型：
--
作者：
Warren, Helen R.;Evangelou, Evangelos;Ehret, Georg B.
高血压是世界范围内心血管疾病的主要遗传危险因素。我们报告了英国生物银行欧洲血统参与者血压（收缩压、舒张压、脉压）的遗传关联，并在其他队列中进行了独立复制，并对107个独立基因座进行了强有力的验证。我们还在先前报道的11个血压位点上发现了新的独立变异。结合一系列计算机功能分析和湿台式实验的结果，我们的发现突出了血管组织中表达基因丰富的血压调节的新生物学途径，并确定了高血压的潜在治疗靶点。遗传风险评分模型的结果提高了通过早期生活方式干预精准医学方法的可能性，以抵消升高血压的遗传变异对未来心血管疾病风险的影响。
Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.