Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
Hum Mol Genet. 2011 Oct 15;20(R2):R158-62. doi: 10.1093/hmg/ddr358. Epub 2011 Aug 29.
The dominant and sometimes competing theories for the aetiology of complex human disease have been the common disease, common variant (CDCV) hypothesis, and the multiple rare variant (MRV) hypothesis. With the advent of genome wide association studies and of second-generation sequencing, we are fortunate in being able to test these ideas. The results to date suggest that these hypotheses are not mutually exclusive. Further, initial evidence suggests that both MRV and CDCV can be true at the same loci, and that other disease-related genetic mechanisms also exist at some of these loci. We propose calling these, pleomorphic risk loci, and discuss here how such loci not only offer understanding of the genetic basis of disease, but also provide mechanistic biological insight into disease processes.
复杂人类疾病病因的主要理论（有时也是竞争理论）一直是常见疾病常见变异（CDCV）假说和多种罕见变异（MRV）假说。随着全基因组关联研究和第二代测序的出现，我们有幸能够检验这些观点。迄今为止的结果表明，这些假设并非互斥。此外，初步证据表明，MRV 和 CDCV 可以在同一基因座上同时成立，并且在这些基因座的某些位置还存在其他与疾病相关的遗传机制。我们建议将这些称为多态风险基因座，并在此讨论这些基因座不仅提供了对疾病遗传基础的理解，还为疾病过程提供了机制生物学见解。
