title: Metabolome-Wide Association Study of Primary Open Angle Glaucoma.
abstract: OBJECTIVE
  To determine if primary open-angle glaucoma (POAG) patients can be differentiated from controls based on metabolic characteristics.
  
  
  METHODS
  We used ultra-high resolution mass spectrometry with C18 liquid chromatography for metabolomic analysis on frozen plasma samples from 72 POAG patients and 72 controls. Metabolome-wide Spearman correlation was performed to select differentially expressed metabolites (DEM) correlated with POAG. We corrected P values for multiple testing using Benjamini and Hochberg false discovery rate (FDR). Hierarchical cluster analysis (HCA) was used to depict the relationship between participants and DEM. Differentially expressed metabolites were matched to the METLIN metabolomics database; both DEM and metabolites significantly correlating with DEM were analyzed using MetaboAnalyst to identify metabolic pathways altered in POAG.
  
  
  RESULTS
  Of the 2440 m/z (mass/charge) features recovered after filtering, 41 differed between POAG cases and controls at FDR = 0.05. Hierarchical cluster analysis revealed these DEM to associate into eight clusters; three of these clusters contained the majority of the DEM and included palmitoylcarnitine, hydroxyergocalciferol, and high-resolution METLIN matches to sphingolipids, other vitamin D-related metabolites, and terpenes. MetaboAnalyst also indicated likely alteration in steroid biosynthesis pathways.
  
  
  CONCLUSIONS
  Global ultrahigh resolution metabolomics emphasized the importance of altered lipid metabolism in POAG. The results suggest specific metabolic processes, such as those involving palmitoylcarnitine, sphingolipids, vitamin D-related compounds, and steroid precursors, may contribute to POAG status and merit more detailed study with targeted methods.
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: L Goodwin
authors.initials: LG
authors.lastname: Burgess
authors.affiliation: Department of Medicine, Emory University Medical Center, Atlanta, Georgia, United States.
authors.forename: Karan
authors.initials: K
authors.lastname: Uppal
authors.affiliation: Department of Medicine, Emory University Medical Center, Atlanta, Georgia, United States.
authors.forename: Douglas I
authors.initials: DI
authors.lastname: Walker
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Roberson
authors.affiliation: Department of Medicine, Emory University Medical Center, Atlanta, Georgia, United States.
authors.forename: ViLinh
authors.initials: V
authors.lastname: Tran
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Megan B
authors.initials: MB
authors.lastname: Parks
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Wade
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Alexandra T
authors.initials: AT
authors.lastname: May
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Allison C
authors.initials: AC
authors.lastname: Umfress
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Jarrell
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Brooklyn O C
authors.initials: BO
authors.lastname: Stanley
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: John
authors.initials: J
authors.lastname: Kuchtey
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Rachel W
authors.initials: RW
authors.lastname: Kuchtey
authors.affiliation: Department of Medicine, Emory University Medical Center, Atlanta, Georgia, United States.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: Vanderbilt Eye Institute Vanderbilt University Medical Center, Nashville, Tennessee, United States.
authors.forename: Milam A
authors.initials: MA
authors.lastname: Brantley
mesh_terms: D000368:Aged; D005136:Eye Proteins / Q000378:metabolism*; D005260:Female; D005902:Glaucoma, Open-Angle / Q000378:metabolism*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome / Q000502:physiology*; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged
chemical_list: D005136:Eye Proteins