Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UK.
Hypertension. 2010 Dec;56(6):1017-1020; discussion 1025. doi: 10.1161/HYPERTENSIONAHA.110.156208.
This brief commentary is based on the debate that took part in May 2010 in New York. We describe the initial difficulties experienced in early genome-wide association studies of blood pressure and hypertension, as well as strategic developments, including large meta-analyses and sampling from the extremes of blood pressure distribution. The reasons for negative attitudes toward the genome-wide association studies include their nonhypothesis-driven character and the need for very large sample sizes. Nevertheless, we describe published successes, which include 13 single nucleotide polymorphisms/loci associated with blood pressure and hypertension at P < 5 x 10⁻⁸, which fulfill the criteria of genome-wide significance. We conclude by suggesting a way forward, which will include resequencing to aid fine mapping and the identification of causal variants, even bigger meta-analyses, and, most importantly, appropriate functional studies leading to clinically useful applications.
这篇简短的述评基于 2010 年 5 月在纽约举行的辩论。我们描述了在血压和高血压的全基因组关联研究早期所经历的初步困难,以及包括大型荟萃分析和从血压分布极端值抽样在内的策略性发展。对全基因组关联研究持否定态度的原因包括其非假设驱动的性质和对非常大数据集的需求。然而,我们描述了已发表的成功案例,其中包括 13 个单核苷酸多态性/基因座与血压和高血压相关,其 P 值小于 5 x 10⁻⁸,达到了全基因组显著性标准。最后,我们提出了一个前进的方向,包括重测序以帮助精细映射和鉴定因果变异,更大规模的荟萃分析,以及最重要的是,适当的功能研究,以实现临床有用的应用。