The metabolomics of asthma control: a promising link between genetics and disease
The objective is to identify novel genetic and biochemical predictors of asthma control using an integrative “omics” approach. We generated lipidomic data by liquid chromatography tandem mass spectrometry (LC‐MS), using plasma samples from 20 individuals with asthma. The outcome of i nterest was a binary indicator of asthma control defined by the use of albuterol inhalers in the preceding week. We integrated metabolomic data with genome‐wide genotype, gene expression, and methylation data of this cohort to identify genomic and molecular indicators of asthma control. A Conditio nal Gaussian Bayesian Network (CGBN) was generated using the strongest predictors from each of these analyses. Integrative and metabolic pathway over‐representation analyses (ORA) identified enrichment of known biological pathways within the strongest molecular determinants. Of the 64 metabolites measured, 32 had known identities. The CGBN model based on four SNPs (rs9522789, rs7147228, rs2701423, rs759582) and two metabolites—monoHETE_0863 and sphingosine‐1‐phosphate (S1P) could predict asthma control with an AUC of 95%. Integrative ORA identified 17 significantly enriched pathways re lated to cellular immune response, interferon signaling, and cytokine‐related signaling, for which arachidonic acid, PGE2 and S1P, in addition to six genes (CHN1, PRKCE, GNA12, OASL, OAS1, and IFIT3) appeared to drive the pathway results. Of these predictors, S1P, GNA12, and PRKCE were enriched in the...
Source: Immunity, Inflammation and Disease - Category: Allergy & Immunology Authors: Michael J. McGeachie,
Amber Dahlin,
Weiliang Qiu,
Damien C. Croteau ‐Chonka,
Jessica Savage,
Ann Chen Wu,
Emily S. Wan,
Joanne E. Sordillo,
Amal Al‐Garawi,
Fernando D. Martinez,
Robert C. Strunk,
Robert F. Lemanske,
Andrew H. Liu,
Benjami Tags: Original Research Source Type: research