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Advances in Psychological Science    2013, Vol. 21 Issue (10) : 1874-1882     DOI: 10.3724/SP.J.1042.2013.01874
Research Methods |
The Comparison of Multiple Testing Corrections Methods in Genome-Wide Association Studies
HUANG Yangyue;KONG Xiangzhen;ZHEN Zonglei;LIU Jia
(State Key Laboratory of Cognitive Science and Learning, Beijing Normal University, Beijing 100875, China)
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Abstract  Genome-Wide Association Studies (GWAS) can reveal the genetic basis of the behavior. However, the association analysis embodies a massive multiple testing problem, where millions of SNPs (Single Nucleotide Polymorphisms) are tested. It is vital to reduce the risk of false positive in multiple testing with an appropriate corrections method. Firstly, Family-Wise Error Rate (FWER) and False Discovery Rate (FDR), the two standard measures of Type I errors in multiple testing were introduced. Secondly, three FWER (i.e., Bonferroni, Holm Step–Down and Permutation) and one FDR (i.e., BH) multiple testing corrections method were discussed from the concept to implementation. Finally, a method to simulate GWAS data was proposed, and the four multiple testing corrections methods were evaluated on the simulated GWAS data. Results showed that SNPs reported without multiple testing corrections had both the highest average hit and the average false alarm. FWER methods reported fewer false alarms, but their average hits were also fewer than that from uncorrected or BH method. In contrast, BH method did well in balance between the false alarm and hit. Furthermore, a comprehensive index, called explained rate, was introduced to evaluate the different methods quantitatively. Results showed BH method had the highest explained rate. In the future GWAS study, researchers would better do multiple testing corrections with BH method.
Keywords Genome-Wide Association Studies      multiple testing corrections      FWER      FDR      simulation     
Corresponding Authors: ZHEN Zonglei   
Issue Date: 15 October 2013
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HUANG Yangyue
KONG Xiangzhen
ZHEN Zonglei
LIU Jia
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HUANG Yangyue,KONG Xiangzhen,ZHEN Zonglei, et al. The Comparison of Multiple Testing Corrections Methods in Genome-Wide Association Studies[J]. Advances in Psychological Science, 2013, 21(10): 1874-1882.
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http://journal.psych.ac.cn/xlkxjz/EN/10.3724/SP.J.1042.2013.01874     OR     http://journal.psych.ac.cn/xlkxjz/EN/Y2013/V21/I10/1874
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