Incorporating prior knowledge to facilitate discoveries in a genome-wide association study on age-related macular degeneration.
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.


RESULTS
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.
Lin
Wan-Yu
WY
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan. wenchung@ntu.edu.tw.
Lee
Wen-Chung
WC