Genome-wide association studies: the key to unlocking neurodegeneration?
Genome-wide association studies: the key to unlocking neurodegeneration?
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DOI：
10.1038/nn.2584
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发表时间：
2010-07-01
影响因子：
25
通讯作者：
Wood, Nicholas W.
中科院分区：
文献类型：
--
作者：
Gandhi, Sonia;Wood, Nicholas W.
成功发现导致罕见单基因疾病的基因已经主导了我们对神经退行性疾病遗传基础的理解。强大的全基因组关联方法的出现有望解释复杂疾病的常见散发形式的遗传病因。除了揭示神经退行性疾病的遗传易感性外，全基因组关联研究（GWASs）也应该成为与疾病发病机制相关的分子的公正发生器。尽管有这种令人兴奋的潜力，但GWAS的结果在一致性和实现这些目标的能力方面各不相同。神经科学家面临的最大挑战是解释GWASs的结果，并将遗传发现转化为在疾病发病机制和最终治疗设计中具有重要生物学意义的功能机制。我们研究了阿尔茨海默病和帕金森病的GWASs的最新结果，并探讨了它们的使用和局限性。我们进一步反思这些结果如何可能加快理解和影响神经变性的分子发病机制的进展。
The successful discovery of genes that cause rare monogenic disorders has dominated our understanding of the genetic basis of neurodegenerative disease. The emergence of robust genome-wide association methodologies promises to explain the genetic etiology of the common sporadic forms of complex diseases. In addition to revealing the genetic susceptibility of neurodegenerative disease, genome-wide association studies (GWASs) should also be an unbiased generator of molecules that are relevant in disease pathogenesis. Despite this exciting potential, GWAS results have varied in their consistency and their ability to deliver these aims. The largest challenge that faces neuroscientists is the interpretation of the results of GWASs and the translation of the genetic findings into functional mechanisms that are biologically important in disease pathogenesis and, ultimately, treatment design. We examine recent results from GWASs of Alzheimer's disease and Parkinson's disease and explore their use and limitations. We further reflect on how these results may expedite progress in understanding and influencing the molecular pathogenesis of neurodegeneration.