King's College London, Department of Medical and Molecular Genetics, 8th floor Tower Wing, Guy's Hospital, London SE19RT, UK.
BMC Genomics. 2011 Feb 1;12:92. doi: 10.1186/1471-2164-12-92.
Genome-wide association studies (GWAS) of common diseases have had a tremendous impact on genetic research over the last five years; the field is now moving from microarray-based technology towards next-generation sequencing. To evaluate the potential of association studies for complex diseases based on exome sequencing we analysed the distribution of association signal with respect to protein-coding genes based on GWAS data for seven diseases from the Wellcome Trust Case Control Consortium.
We find significant concentration of association signal in exons and genes for Crohn's Disease, Type 1 Diabetes and Bipolar Disorder, but also observe enrichment from up to 40 kilobases upstream to 40 kilobases downstream of protein-coding genes for Crohn's Disease and Type 1 Diabetes; the exact extent of the distribution is disease dependent.
Our work suggests that exome sequencing may be a feasible approach to find genetic variation associated with complex disease. Extending the exome sequencing to include flanking regions therefore promises further improvement of covering disease-relevant variants.
全基因组关联研究（GWAS）在过去五年中对遗传研究产生了巨大影响；该领域现在正从基于微阵列的技术向下一代测序发展。为了评估基于外显子组测序的复杂疾病关联研究的潜力，我们根据来自威康信托基金会病例对照联盟的七种疾病的 GWAS 数据，分析了关联信号在蛋白编码基因方面的分布。
我们发现克罗恩病、1 型糖尿病和双相情感障碍的关联信号在外显子和基因中显著集中，但也观察到克罗恩病和 1 型糖尿病的蛋白编码基因上游达 40kb 至下游达 40kb 的区域富集；分布的确切范围取决于疾病。
我们的工作表明，外显子组测序可能是一种可行的方法，用于寻找与复杂疾病相关的遗传变异。因此，将外显子组测序扩展到包含侧翼区域有望进一步提高对疾病相关变异的覆盖。
Zotero 插件
