Lipids in Health and Disease (Nov 2024)

Associations of human blood metabolome with optic neurodegenerative diseases: a bi-directionally systematic mendelian randomization study

  • Bin Tong,
  • Chubing Long,
  • Jing Zhang,
  • Xin Zhang,
  • Zhengyang Li,
  • Haodong Qi,
  • Kangtai Su,
  • Deju Zhang,
  • Yixuan Chen,
  • Jitao Ling,
  • Jianping Liu,
  • Yunwei Hu,
  • Peng Yu

DOI
https://doi.org/10.1186/s12944-024-02337-0
Journal volume & issue
Vol. 23, no. 1
pp. 1 – 13

Abstract

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Abstract Background Metabolic disruptions were observed in patients with optic neurodegenerative diseases (OND). However, evidence for the causal association between metabolites and OND is limited. Methods Two-sample Mendelian randomization (MR). Summary data for 128 blood metabolites was selected from three genome-wide association study (GWASs) involving 147,827 participants of European descent. GWASs Data for glaucoma (20906 cases and 391275 controls) and age-related macular degeneration (AMD, 9721 cases and 381339 controls) came from FinnGen consortium. A bi-directional MR was conducted to assess causality, and a Mediation MR was further applied to explore the indirect effect, a phenome-wide MR analysis was then performed to identify possible side-effects of the therapies. Results All the results underwent correction for multiple testing and rigorous sensitivity analyses. We identified N-acetyl glycine, serine, uridine were linked to an elevated risk of glaucoma. 1-arachidonic-glycerol-phosphate-ethanolamine, 4-acetamido butanoate, o-methylascorbate, saturated fatty acids, monounsaturated fatty acids, VLDL cholesterol, serum total cholesterol, X-11,529 were linked to reduced risk of glaucoma. There were 4 metabolites linked to a reduced risk of AMD, including tryptophan betaine, 4-androsten-3beta-17beta-diol disulfate, apolipoprotein B, VLDL cholesterol. We discovered IOP, AS, T2D as glaucoma risk factors, while BMI, AS, GCIPL as AMD factors. And 6 metabolites showed associations with risk factors in the same direction as their associations with glaucoma/AMD. Phenome-wide MR indicated that selected metabolites had protective/adverse effects on other diseases. Conclusions By integrating genomics and metabolomics, this study supports new insights into the intricate mechanisms, and helps prevent and screen glaucoma and AMD.

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