Genetic epidemiological studies of coronary heart disease.
Genetic epidemiological studies of coronary heart disease.
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冠心病的遗传流行病学研究。
DOI：
10.1093/ije/31.4.730
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发表时间：
2002
影响因子：
7.7
通讯作者：
B. Keavney
中科院分区：
文献类型：
--
作者：
B. Keavney
最近公布的人类基因组序列被广泛认为为我们对各种常见人类疾病的理解提供了一个彻底改变的机会。一个特别的希望是，从基因组测序工作中获得的新信息将促进群体遗传研究的开展，这将发现导致“复杂”或“多基因”（即由多个基因的作用引起）疾病的遗传变异。在这篇综述中，我试图把这种愿望纳入冠心病（CHD）的观点。首先，我考虑到目前为止所知道的关于冠心病的“遗传结构”。其次，我讨论了这种“遗传结构”以及某些种群遗传问题对研究设计的影响。第三，我考虑了迄今为止冠心病遗传流行病学研究结果往往存在差异的原因，并探讨了未来提高此类研究可靠性的策略。最后，我考虑了足够规模的遗传流行病学研究如何能够很好地解决关于假设的冠心病新危险因素的致病性质的特别重要和困难的争议。在遗传学家和流行病学家的思想中，对复杂疾病（如冠心病）的基因研究占据中心位置的原因有很多。首先，基因研究提供了确定疾病的决定因素的机会，这些决定因素很可能是致病的。这是因为基因型在整个生命过程中都是不变的，因此不容易通过与疾病本身存在或身体对疾病的反应相关的机制（例如，测量血浆中假设的风险因素的方式）进行混淆。其次，目前治疗复杂疾病的药理学装备包括作用于人类基因组中大约3万个基因中的极少数（几百个）的药物。因此，鉴定导致冠心病风险的新基因可能会带来具有强大分子基础的新治疗靶点。第三，识别风险基因型可能比目前通过测量已知风险因素更准确地确定个人患冠心病的风险。这部分是因为基因型可以测量新的或以其他方式无法测量的生物途径的活性，部分是因为与血浆和其他定量表型风险因素的测量相比，基因型不容易受到短期波动和测量误差的影响。
The recent publication of the human genome sequence is widely thought to offer the opportunity for a radical change in our understanding of a variety of common human diseases. One particular hope is that the new information available from the genome sequencing effort will facilitate the conduct of population genetic studies, which will discover the genetic variants responsible for ‘complex’ or ‘polygenic’ (i.e. resulting from the action of more than one gene) diseases. In this review I attempt to put this aspiration into perspective for coronary heart disease (CHD). Firstly, I consider what is known thus far regarding the ‘genetic architecture’ of CHD. Secondly, I discuss the implications of this ‘genetic architecture‘, and of certain population genetic issues, for study design. Thirdly, I consider the reasons why the results of genetic-epidemiological studies of CHD to date have tended to be discrepant, and explore strategies for increasing the reliability of such studies in the future. Finally, I consider how genetic-epidemiological studies of adequate size may be uniquely well placed to resolve particularly important and difficult controversies regarding the causative nature of hypothesized novel risk factors for CHD. There are a number of reasons why genetic studies of complex diseases such as CHD have moved to a central position in the thinking of both geneticists and epidemiologists. Firstly, genetic studies offer the opportunity to identify determinants of disease that are very likely to be causative. This is because genotypes are unchanged throughout life, and therefore not susceptible to confounding via mechanisms related either to the presence of disease itself or the body’s response to disease (in the way that measurement of hypothesized risk factors in plasma, for example, could be). Secondly, the current pharmacological armamentarium for complex diseases consists of drugs which act on a very small number (several hundred) of the 30 000 or so genes in the human genome. Identification of novel genes that contribute to CHD risk could therefore lead to new therapeutic targets with strong molecular underpinning. Thirdly, identification of risk genotypes might enable more accurate determination of an individual’s risk of CHD than is currently possible from measurement of known risk factors. This is partly because genotypes could measure the activity of novel or otherwise unmeasurable biological pathways, and partly because genotypes would not be susceptible to short-term fluctuations and measurement error, in contrast to measurements of plasma and other quantitative phenotypic risk factors.
人类脂蛋白脂肪酶基因内的分支结构及其对表型关联研究的影响。
影响因子：
3.3
作者：
Templeton,AR;Weiss,KM;Nickerson,DA;Boerwinkle,E;Sing,CF
通讯作者：
Sing,CF
影响因子：
158.5
作者：
MARENBERG, ME;RISCH, N;DEFAIRE, U
通讯作者：
DEFAIRE, U
影响因子：
3.5
作者：
McKenzie, CA;Abecasis, GR;Cardon, LR
通讯作者：
Cardon, LR