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- Title
On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies.
- Authors
Petersen, Ann-Kristin; Krumsiek, Jan; W�gele, Brigitte; Theis, Fabian J.; Wichmann, H-Erich; Gieger, Christian; Shure, Karsten
- Abstract
Background: Genome-wide association studies (GWAS) with metabolic traits and metabolome-wide association studies (MWAS) with traits of biomedical relevance are powerful tools to identify the contribution of genetic,environmental and lifestyle factors to the etiology of complex diseases. Hypothesis-free testing of ratios between all possible metabolite pairs in GWAS and MWAS has proven to be an innovative approach in the discovery of new biologically meaningful associations. The p-gain statistic was introduced as an ad-hoc measure to determine whether a ratio between two metabolite concentrations carries more information than the two corresponding metaboliteconcentrations alone. So far, only a rule of thumb was applied to determine the significance of the p-gain.Results: Here we explore the statistical properties of the p-gain through simulation of its density and by sampling of experimental data. We derive critical values of the p-gain for different levels of correlation between metabolite pairs and show that B/(2*α) is a conservative critical value for the p-gain, where α is the level of significance and B the number of tested metabolite pairs.Conclusions: We show that the p-gain is a well defined measure that can be used to identify statistically significantmetabolite ratios in association studies and provide a conservative significance cut-off for the p-gain for use in future association studies with metabolic traits.
- Subjects
METABOLITES; CHEMICAL ecology; METABOLOMICS; GENOMES; GENOMICS
- Publication
BMC Bioinformatics, 2012, Vol 13, Issue 1, p120
- ISSN
1471-2105
- Publication type
Article
- DOI
10.1186/1471-2105-13-120