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ORIGINAL RESEARCH article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1391999

Systemic inflammatory regulators and age-related macular degeneration: A bidirectional Mendelian randomization study

Provisionally accepted
Xi Liu Xi Liu 1,2Yu Cao Yu Cao 3Ying Wang Ying Wang 4Lihua Kang Lihua Kang 1,2Guowei Zhang Guowei Zhang 1,2Junfang Zhang Junfang Zhang 1,2Bai Qin Bai Qin 1,2Ling Yang Ling Yang 1,2Jiawei Luo Jiawei Luo 1,2Pengfei Li Pengfei Li 1,2Wenjing Geng Wenjing Geng 1,2Min Ji Min Ji 1,2Huaijin Guan Huaijin Guan 1,2*
  • 1 Nantong University, Nantong, China
  • 2 Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
  • 3 Third Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
  • 4 Affiliated Hospital of Yangzhou University, Yangzhou, Jiangsu Province, China

The final, formatted version of the article will be published soon.

    We investigated the relationship between systematic regulators of inflammation and the risk of age-related macular degeneration (AMD), both wet and dry forms, by using bidirectional, two-sample Mendelian randomization (MR). We performed bidirectional two-sample Mendelian randomization analysis using genome-wide study (GWAS) data for 91 plasma proteins from 14,824 individuals of European descent across 11 study groups. Next, we utilized data from the FinnGen consortium to study AMD using the inverse-variance-weighted approach for Mendelian randomization.Additional analyses involved MR-Egger, Weighted median, Weighted mode, MR-PRESSO, and MR-Steiger filtering techniques. We identified 16 cytokines associated AMD outcomes and post FDR correction, higher levels of fibroblast growth factor 19 and leukemia inhibitory factor receptor were associated with decreased risk for AMD, while higher levels of tumour necrosis factor ligand superfamily member 14 were associated with increased risk for AMD. Additionally, higher levels of interleukin-10 receptor subunit alpha were associated with decreased risk for wet AMD, higher levels of leukemia inhibitory factor receptor were associated with decreased risk for dry AMD, and higher levels of signaling lymphocytic activation molecule were associated with increased risk for dry AMD. Genetic susceptibility to AMD was associated with elevated levels of TNF-related activation-induced cytokines (TNFSF11), and genetic susceptibility to wet AMD was associated with elevated levels of TNFSF11, interleukin-18 receptor 1 (IL18R1), and CUB domain-containing protein 1 (CDCP1). This research enhances our understanding of systemic inflammation in AMD, providing insights into etiology, diagnosis, and treatment of AMD and its forms.

    Keywords: Cytokines, age-related macular degeneration, Mendelian randomization, Inflammation, GWAS

    Received: 16 May 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Liu, Cao, Wang, Kang, Zhang, Zhang, Qin, Yang, Luo, Li, Geng, Ji and Guan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Huaijin Guan, Nantong University, Nantong, China

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