整合先验知识以促进年龄相关性黄斑变性全基因组关联研究中的发现。
Incorporating prior knowledge to facilitate discoveries in a genome-wide association study on age-related macular degeneration.
作者信息
Lin Wan-Yu, Lee Wen-Chung
机构信息
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan.
出版信息
BMC Res Notes. 2010 Jan 28;3:26. doi: 10.1186/1756-0500-3-26.
BACKGROUND
Substantial genotyping data produced by current high-throughput technologies have brought opportunities and difficulties. With the number of single-nucleotide polymorphisms (SNPs) going into millions comes the harsh challenge of multiple-testing adjustment. However, even with the false discovery rate (FDR) control approach, a genome-wide association study (GWAS) may still fall short of discovering any true positive gene, particularly when it has a relatively small sample size.
FINDINGS
To counteract such a harsh multiple-testing penalty, in this report, we incorporate findings from previous linkage and association studies to re-analyze a GWAS on age-related macular degeneration. While previous Bonferroni correction and the traditional FDR approach detected only one significant SNP (rs380390), here we have been able to detect seven significant SNPs with an easy-to-implement prioritized subset analysis (PSA) with the overall FDR controlled at 0.05. These include SNPs within three genes: CFH, CFHR4, and SGCD.
CONCLUSIONS
Based on the success of this example, we advocate using the simple method of PSA to facilitate discoveries in future GWASs.
背景
当前高通量技术产生的大量基因分型数据带来了机遇和困难。随着单核苷酸多态性（SNP）数量达到数百万，多重检验校正面临严峻挑战。然而，即使采用错误发现率（FDR）控制方法，全基因组关联研究（GWAS）仍可能无法发现任何真正的阳性基因，尤其是在样本量相对较小时。
研究结果
为了应对如此严峻的多重检验惩罚，在本报告中，我们结合先前连锁和关联研究的结果，重新分析了一项关于年龄相关性黄斑变性的GWAS。虽然先前的Bonferroni校正和传统的FDR方法仅检测到一个显著的SNP（rs380390），但在此我们能够通过易于实施的优先子集分析（PSA）检测到七个显著的SNP，总体FDR控制在0.05。这些SNP包括三个基因内的SNP：CFH、CFHR4和SGCD。
结论
基于这个例子的成功，我们提倡使用简单的PSA方法来促进未来GWAS中的发现。
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