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Significance Levels in Genome‐Wide Interaction Analysis (GWIA)
Author(s) -
Becker Tim,
Herold Christine,
Meesters Christian,
Mattheisen Manuel,
Baur Max P.
Publication year - 2011
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2010.00610.x
Subject(s) - type i and type ii errors , genome wide association study , missing heritability problem , genetics , genome , multiple comparisons problem , single nucleotide polymorphism , computational biology , biology , statistical power , computer science , statistics , mathematics , gene , genotype
Summary Interaction between genetic variants is hypothesized to be one of several putative explanations for the ‘case of missing heritability.’ Therefore, Genome‐Wide Interaction Analysis (GWIA) has recently gained substantial interest. GWIA is computationally challenging and respective power type I error studies are particularly difficult. Therefore, an accepted significance level for GWIA studies does not currently exist. It has been shown that for a GWAS single‐marker analysis with n SNPs a correction for multiple testing with 1/2 · n is appropriate for populations of European ancestry. We speculated that for GWIA, correction by 1/4 · m should be appropriate, where m = n · ( n − 1)/2 is the number of SNP pairs. We tried to verify this hypothesis using the INTERSNP program that implements interaction analysis and genome‐wide Monte‐Carlo (MC) simulation. Using a type I error study based on Illumina ® HumanHap 550 data, we were able to reproduce the published result for single‐marker analysis. For GWIA using a test for allelic interaction, we show that correction with roughly 0.4 · m is appropriate, a number that is somewhat larger than that of our hypothesis. In summary, it can be stated that for an Illumina ® ‐type marker panel with 500,000 SNPs, an uncorrected P‐value of 1.0 × 10 −12 is needed to establish genome‐wide significance at the 0.05 level.