Liu Xi, Cao Yu, Wang Ying, Kang Lihua, Zhang Guowei, Zhang Junfang, Qin Bai, Yang Ling, Luo Jiawei, Li Pengfei, Geng Wenjing, Ji Min, Guan Huaijin
Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China.
Department of Medicine, Nantong University, Nantong, Jiangsu, China.
Front Genet. 2024 Dec 13;15:1391999. doi: 10.3389/fgene.2024.1391999. eCollection 2024.
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.
我们通过双向双样本孟德尔随机化（MR）研究了炎症的系统性调节因子与湿性和干性年龄相关性黄斑变性（AMD）风险之间的关系。
我们使用来自11个研究组的14824名欧洲血统个体的91种血浆蛋白的全基因组研究（GWAS）数据进行双向双样本孟德尔随机化分析。接下来，我们利用芬兰基因组联盟的数据，采用孟德尔随机化的逆方差加权方法研究AMD。额外的分析涉及MR-Egger、加权中位数、加权模式、MR-PRESSO和MR-Steiger过滤技术。
我们确定了16种与AMD结局相关的细胞因子，经FDR校正后，成纤维细胞生长因子19和白血病抑制因子受体水平较高与AMD风险降低相关，而肿瘤坏死因子配体超家族成员14水平较高与AMD风险增加相关。此外，白细胞介素-10受体亚基α水平较高与湿性AMD风险降低相关，白血病抑制因子受体水平较高与干性AMD风险降低相关，信号淋巴细胞激活分子水平较高与干性AMD风险增加相关。AMD的遗传易感性与TNF相关激活诱导细胞因子（TNFSF11）水平升高有关，湿性AMD的遗传易感性与TNFSF11、白细胞介素-18受体1（IL18R1）和含CUB结构域蛋白1（CDCP1）水平升高有关。
本研究增进了我们对AMD中全身炎症的理解，为AMD及其亚型的病因、诊断和治疗提供了见解。
