Prediagnostic Plasma Metabolomics and the Risk of Exfoliation Glaucoma.
Kang Jae H, Zeleznik Oana, Frueh Lisa, Lasky-Su Jessica, Eliassen A Heather, Clish Clary, Rosner Bernard A, Pasquale Louis R, Wiggs Janey L
AI Summary
This study found specific plasma metabolites, including lysophosphatidylcholines, plasmalogens, triacylglycerols, and steroids, were associated with exfoliation glaucoma risk over a decade before diagnosis, suggesting potential early biomarkers.
Abstract
Purpose
The etiology of exfoliation glaucoma (XFG) is poorly understood. We aimed to identify a prediagnostic plasma metabolomic signature associated with XFG.
Methods
We conducted a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study. We collected blood samples in 1989-1990 (Nurses' Health Study) and 1993-1995 (Health Professionals Follow-up Study). We identified 205 incident XFG cases through 2016 (average time to diagnosis from blood draw = 11.8 years) who self-reported glaucoma and were confirmed as XFG cases with medical records. We profiled plasma metabolites using liquid chromatography-mass spectrometry. We evaluated 379 known metabolites (transformed for normality using probit scores) using multiple conditional logistic models. Metabolite set enrichment analysis was used to identify metabolite classes associated with XFG. To adjust for multiple comparisons, we used number of effective tests (NEF) and the false discovery rate (FDR).
Results
Mean age of cases (n = 205) at diagnosis was 71 years; 85% were women and more than 99% were Caucasian; controls (n = 205) reported eye examinations as of the matched cases' index date. Thirty-three metabolites were nominally significantly associated with XFG (P < 0.05), and 4 metabolite classes were FDR-significantly associated. We observed positive associations for lysophosphatidylcholines (FDR = 0.02) and phosphatidylethanolamine plasmalogens (FDR = 0.004) and inverse associations for triacylglycerols (FDR < 0.0001) and steroids (FDR = 0.03). In particular, the multivariable-adjusted odds ratio with each 1 standard deviation higher plasma cortisone levels was 0.49 (95% confidence interval, 0.32-0.74; NEF = 0.05).
Conclusions
In plasma from a decade before diagnosis, lysophosphatidylcholines and phosphatidylethanolamine plasmalogens were positively associated and triacylglycerols and steroids (e.g., cortisone) were inversely associated with XFG risk.
MeSH Terms
Shields Classification
Key Concepts6
In a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study, 33 metabolites were nominally significantly associated with exfoliation glaucoma (XFG) (P < 0.05).
In a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study, lysophosphatidylcholines were positively associated with exfoliation glaucoma (XFG) risk (FDR = 0.02).
In a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study, phosphatidylethanolamine plasmalogens were positively associated with exfoliation glaucoma (XFG) risk (FDR = 0.004).
In a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study, triacylglycerols were inversely associated with exfoliation glaucoma (XFG) risk (FDR < 0.0001).
In a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study, steroids were inversely associated with exfoliation glaucoma (XFG) risk (FDR = 0.03).
In a 1:1 matched case-control study nested within the Nurses' Health Study and Health Professionals Follow-up Study, the multivariable-adjusted odds ratio for exfoliation glaucoma (XFG) with each 1 standard deviation higher plasma cortisone levels was 0.49 (95% confidence interval, 0.32-0.74; NEF = 0.05).
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