On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies

Petersen, Ann-Kristin; Krumsiek, Jan; Waegele, Brigitte; Theis, Fabian J.; Wichmann, H-Erich; Gieger, Christian und Suhre, Karsten (2012): On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies. In: BMC Bioinformatics 13:120

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 metabolite concentrations 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*alpha) is a conservative critical value for the p-gain, where a 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 significant metabolite ratios in association studies and provide a conservative significance cut-off for the p-gain for use in future association studies with metabolic traits.

• Dokumententyp: Zeitschriftenartikel
• Publikationsform: Publisher's Version
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1471-2105
• Sprache: Englisch