{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T15:39:50Z","timestamp":1774625990820,"version":"3.50.1"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Bioinformatics"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>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*\u03b1) is a conservative critical value for the p-gain, where \u03b1 is the level of significance and B the number of tested metabolite pairs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2105-13-120","type":"journal-article","created":{"date-parts":[[2012,6,15]],"date-time":"2012-06-15T11:43:55Z","timestamp":1339760635000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":123,"title":["On the hypothesis-free testing of metabolite ratios in genome-wide and metabolome-wide association studies"],"prefix":"10.1186","volume":"13","author":[{"given":"Ann-Kristin","family":"Petersen","sequence":"first","affiliation":[]},{"given":"Jan","family":"Krumsiek","sequence":"additional","affiliation":[]},{"given":"Brigitte","family":"W\u00e4gele","sequence":"additional","affiliation":[]},{"given":"Fabian J","family":"Theis","sequence":"additional","affiliation":[]},{"given":"H-Erich","family":"Wichmann","sequence":"additional","affiliation":[]},{"given":"Christian","family":"Gieger","sequence":"additional","affiliation":[]},{"given":"Karsten","family":"Suhre","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2012,6,6]]},"reference":[{"issue":"9","key":"5556_CR1","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.4155\/bio.09.158","volume":"1","author":"J Han","year":"2009","unstructured":"Han J, Datla R, Chan S, Borchers CH: Mass spectrometry-based technologies for high-throughput metabolomics. 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