Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Department of Psychological Medicine and Neurology, School of Medicine, Cardiff University, Cardiff, UK.
Int J Geriatr Psychiatry. 2011 Aug;26(8):793-802. doi: 10.1002/gps.2628. Epub 2010 Oct 19.
Alzheimer's disease (AD) is highly heritable, but genetically complex. Recently, three large-scale genome-wide association studies have made substantial breakthroughs in disentangling the genetic architecture of the disease. These studies combined include data from over 43 000 independent individuals and provide compelling evidence that variants in four novel susceptibility genes (CLU, PICALM, CR1, BIN1) are associated with disease risk. These findings are tremendously exciting, not only in providing new avenues for exploration, but also highlighting the potential for further gene discovery when larger samples are analysed. Here we discuss progress to date in identifying risk genes for dementia, ways forward and how current findings are refining previous ideas and defining new putative primary disease mechanisms.
阿尔茨海默病（AD）具有高度遗传性，但遗传复杂。最近，三项大规模全基因组关联研究在解析该疾病的遗传结构方面取得了重大突破。这些研究结合了超过 43000 名独立个体的数据，并提供了令人信服的证据，表明四个新的易感性基因（CLU、PICALM、CR1、BIN1）中的变异与疾病风险相关。这些发现令人非常兴奋，不仅为探索提供了新的途径，而且当分析更大的样本时，还突出了进一步发现基因的潜力。在这里，我们讨论了迄今为止在确定痴呆风险基因方面的进展、前进的方向以及当前的发现如何改进以前的想法并定义新的潜在主要疾病机制。
