Investigating SM Ratios in Targeted Metabolomics

For the investigation of SM ratios measured by targeted metabolomics using the Biocrates P180 kit, we used the same cohort data and statistical models used in Toledo et al.^{20 (link)}. For the selection of the most informative SM ratio, we first calculated all ratios between short-chain (chain length < C20) and long-chain (≥C20) SMs on metabolite levels not adjusted for medication. For each ratio, we then identified significant medications using backward selection based on the Bayesian Information Criterion. Significant medications were included as additional covariates extending the base models described in Toledo et al.^{20 (link)} for phenotype associations. Using the Pgain criterion, which is defined by the ratio of the minimum association p-value of the constituents of a ratio with the association p-value of the ratio and provides a measure of significance added by the ratio, we obtained the ratio of SM (d34:1) and SM (d43:1) as the one with the largest overall Pgain.

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Baloni P., Arnold M., Buitrago L., Nho K., Moreno H., Huynh K., Brauner B., Louie G., Kueider-Paisley A., Suhre K., Saykin A.J., Ekroos K., Meikle P.J., Hood L., Price N.D., Doraiswamy P.M., Funk C.C., Hernández A.I., Kastenmüller G., Baillie R., Han X, & Kaddurah-Daouk R. (2022). Multi-Omic analyses characterize the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer’s disease. Communications Biology, 5, 1074.

Publication 2022

P180 kit

Medications Phenotype

Corresponding Organization : The University of Texas Health Science Center at San Antonio

Other organizations : Institute for Systems Biology, Helmholtz Zentrum München, SUNY Downstate Health Sciences University, Indiana University – Purdue University Indianapolis, Baker Heart and Diabetes Institute, Weill Cornell Medical College in Qatar, Cornell University, Erasmus University Rotterdam, Erasmus MC, Leiden University, Ollscoil na Gaillimhe – University of Galway, University of Alberta, University of California, Davis, University of Hawaiʻi at Mānoa, University of Pennsylvania

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Variable analysis

independent variables

Ratio of short-chain (chain length < C20) and long-chain (≥C20) sphingomyelins (SMs)
Significant medications identified using backward selection based on the Bayesian Information Criterion

dependent variables

Phenotype associations

control variables

Metabolite levels not adjusted for medication

controls

No positive or negative controls were explicitly mentioned in the provided information.

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