Genome-based prediction of common diseases: advances and prospects
Genome-based prediction of common diseases: advances and prospects
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DOI：
10.1093/hmg/ddn250
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发表时间：
2008-10-15
影响因子：
3.5
通讯作者：
van Duijn, Cornelia M.
中科院分区：
文献类型：
--
作者：
Janssens, A. Cecile J. W.;van Duijn, Cornelia M.
常见疾病，如2型糖尿病和冠心病，是遗传和环境因素复杂相互作用的结果。基因组学研究的最新进展促进了易感基因的发现，并推动了对个性化医疗的遗传图谱机会的期望。个性化医疗需要一种相当准确地预测疾病风险的测试，特别是当干预是侵入性的、昂贵的或有重大副作用的时候。目前，仅基于多种遗传变异或结合传统疾病危险因素对常见病进行预测的研究显示预测价值有限，但都只研究了有限数量的易感变异。来自全基因组关联研究的新基因发现肯定会进一步改善对常见疾病的预测，但问题是这种改善是否足以实现个性化医疗。在本文中，我们认为，新的基因发现可能不会明显提高常见疾病的预测到一定程度，它将改变个人在增加风险的管理。只有当我们能够像理解单基因疾病那样理解常见疾病的完整因果机制时，才有望取得实质性进展。基因组学研究将有助于这种理解，但复杂疾病的复杂性可能最终会限制对无症状个体的疾病进行准确预测的机会，因为揭示其完整的因果途径可能是不可能的。
Common diseases such as type 2 diabetes and coronary heart disease result from a complex interplay of genetic and environmental factors. Recent developments in genomics research have boosted progress in the discovery of susceptibility genes and fueled expectations about opportunities of genetic profiling for personalizing medicine. Personalized medicine requires a test that fairly accurately predicts disease risk, particularly when interventions are invasive, expensive or have major side effects. Recent studies on the prediction of common diseases based on multiple genetic variants alone or in addition to traditional disease risk factors showed limited predictive value so far, but all have investigated only a limited number of susceptibility variants. New gene discoveries from genome-wide association studies will certainly further improve the prediction of common diseases, but the question is whether this improvement is sufficient to enable personalized medicine. In this paper, we argue that new gene discoveries may not evidently improve the prediction of common diseases to a degree that it will change the management of individuals at increased risk. Substantial improvements may only be expected if we manage to understand the complete causal mechanisms of common diseases to a similar extent as we understand those of monogenic disorders. Genomics research will contribute to this understanding, but it is likely that the complexity of complex diseases may ultimately limit the opportunities for accurate prediction of disease in asymptomatic individuals as unraveling their complete causal pathways may be impossible.