Thomas Gilles
Synergie Lyon Cancer, 150, cours Albert Thomas, 69008 Lyon, France.
Med Sci (Paris). 2009 Mar;25 Spec No 1:42-4. doi: 10.1051/medsci/2009251s42.
The genome-wide association approach has been the most powerful and efficient study design thus far in identifying genetic variants that are associated with complex human diseases. This approach became feasible as the result of several key advancements in genetic knowledge, genotyping technologies, statistical analysis algorithms and the availability of large collections of cases and controls. With all these necessary tools in hand, many genome-wide association studies were recently completed, and many more studies which will explore the genetic basis of various complex diseases and quantitative traits are soon to come. The recent large genotyping studies have identified a new repertoire of cancer susceptibility genes and loci which are characterized by common risk alleles. Many of these loci were detected at low power, indicating that many further loci will probably be detected with larger studies. For the most part, the loci were not previously suspected to be related to carcinogenesis, and point to new disease mechanisms. The risks conferred by the susceptibility alleles are low, generally 1.3-fold or less. The combined effects may, however, be sufficiently large to be useful for risk prediction, and targeted screening and prevention, particularly as more loci are identified.
全基因组关联研究方法是迄今为止在识别与复杂人类疾病相关的基因变异方面最强大、最有效的研究设计。由于遗传知识、基因分型技术、统计分析算法方面的几项关键进展以及大量病例和对照样本库的可得性,这种方法变得可行。有了所有这些必要工具,最近完成了许多全基因组关联研究,而且更多探索各种复杂疾病和数量性状遗传基础的研究也即将开展。最近的大型基因分型研究已经确定了一组新的癌症易感基因和位点,其特征是常见风险等位基因。其中许多位点是在低效能情况下检测到的,这表明通过更大规模的研究可能会检测到更多的位点。在很大程度上,这些位点以前并未被怀疑与致癌作用有关,它们指向新的疾病机制。易感等位基因带来的风险较低,一般为1.3倍或更低。然而,综合效应可能足够大,可用于风险预测以及靶向筛查和预防,特别是随着更多位点被识别出来。