Plasma metabolite profile for primary open-angle glaucoma in three US cohorts and the UK Biobank

Author(s): Oana A Zeleznik ° (1,2), Jae H Kang ° (3,4), Jessica Lasky-Su (3,4), A Heather Eliassen (3,4,5,6), Lisa Frueh (3), Clary B Clish (7), Bernard A Rosner (3,4,8), Tobias Elze (4,9), Pirro Hysi (10,11,12), Anthony Khawaja (13,14), Janey L Wiggs (4,15), Louis R Pasquale (16); UK Biobank Eye and Vision Consortium

1 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. ozeleznik@bwh.harvard.edu.
2 Department of Medicine, Harvard Medical School, Boston, MA, USA. ozeleznik@bwh.harvard.edu.
3 Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
4 Department of Medicine, Harvard Medical School, Boston, MA, USA.
5 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
6 Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
7 Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
8 Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
9 Department of Ophthalmology, Schepens Research Eye Institute of Massachusetts Eye and Ear, Boston, MA, USA.
10 Department of Ophthalmology, King's College London, London, UK.
11 Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
12 St. Thomas' Hospital, London, UK.
13 National Institute for Health and Care Research Biomedical Research Centre, Moorfields Eye Hospital, London, UK.
14 National Institute for Health and Care Research Biomedical Research Centre, Institute of Ophthalmology, University College London, London, UK.
15 Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA.
16 Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

° contributed equally

Glaucoma is a progressive optic neuropathy and a leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is the most common form, and yet the etiology of this multifactorial disease is poorly understood. We aimed to identify plasma metabolites associated with the risk of developing POAG in a case-control study (599 cases and 599 matched controls) nested within the Nurses' Health Studies, and Health Professionals' Follow-Up Study. Plasma metabolites were measured with LC-MS/MS at the Broad Institute (Cambridge, MA, USA); 369 metabolites from 18 metabolite classes passed quality control analyses.

For comparison, in a cross-sectional study in the UK Biobank, 168 metabolites were measured in plasma samples from 2,238 prevalent glaucoma cases and 44,723 controls using NMR spectroscopy (Nightingale, Finland; version 2020). Here we show higher levels of diglycerides and triglycerides are adversely associated with glaucoma in all four cohorts, suggesting that they play an important role in glaucoma pathogenesis.

Nat Commun. 2023 May 19;14(1):2860. doi: 10.1038/s41467-023-38466-w.

PMID: 37208353 PMCID: PMC10199010 DOI: 10.1038/s41467-023-38466-w

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