Genetic variation reveals the influence of steroid hormones on the risk of retinal neurodegenerative diseases

Kangcheng Liu; Huimin Fan; Hanying Hu; Yanhua Cheng; Jingying Liu; Zhipeng You

doi:10.3389/fendo.2022.1088557

Genetic variation reveals the influence of steroid hormones on the risk of retinal neurodegenerative diseases

Front Endocrinol (Lausanne). 2023 Jan 10:13:1088557. doi: 10.3389/fendo.2022.1088557. eCollection 2022.

Authors

Kangcheng Liu¹, Huimin Fan¹, Hanying Hu¹, Yanhua Cheng¹, Jingying Liu¹, Zhipeng You¹

Affiliation

¹ Jiangxi Province Division of National Clinical Research Center for Ocular Diseases, Jiangxi Clinical Research Center for Ophthalmic Disease, Jiangxi Research Institute of Ophthalmology and Visual Science, Affiliated Eye Hospital of Nanchang University, Nanchang, China.

Abstract

It is difficult to get evidence from randomized trials of a causal relationship between steroid hormones produced by the adrenal gland and gonad and retinal neurodegenerative disorders (RND). In this study, genetic variations of aldosterone (Aldo), androstenedione (A4), progesterone (P4), hydroxyprogesterone (17-OHP), and testosterone/17β-estradiol (T/E2) were obtained from genome-wide association studies as instrumental variables. Mendelian randomization (MR) analysis was used to assess the impact on the risk of RND, including glaucoma (8,591 cases and 210,201 controls), diabetic retinopathy (DR, 14,584 cases and 202,082 controls) and age-related macular degeneration (AMD, 14,034 cases and 91,214 controls). As the main method, inverse variance weighted results suggest that the increased glaucoma risk was affected by T/E2 (OR = 1.11, 95% CI, 1.01-1.22, P = 0.03), which was further validated by other methods (P_WM = 0.03, P_MLE = 0.03, P_MR-RAPS ₌ 0.03). In the replicated stage, the causal relationship between T/E2 and glaucoma was verified based on the MRC-IEU consortium (P = 0.04). No impact of Aldo, A4, P4, 17-OHP, and T/E2 was observed for the risk of DR (P > 0.05) and AMD (P > 0.05). The heterogeneity test (P > 0.05) and pleiotropy test (P > 0.05) verified the robustness of the results. Our results suggest that T/E2 has a suggestive effect on the glaucoma risk. However, the genetic evidence based on a large sample does not support the effect of steroid hormones on DR and AMD risk. Further studies are vital to assess the possibility of steroid hormones as targets for prevention and treatment.

Keywords: Mendelian randomization; causality; glaucoma; retinal neurodegenerative disease; steroid hormones.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldosterone
Estradiol
Genetic Variation
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Neurodegenerative Diseases*
Retinal Diseases*
Steroids

Substances

Aldosterone
Estradiol
Steroids

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (81860175, 8226040184) and, Science and Technology Innovation Base Construction - Clinical Medicine Research Centre Project (20221ZDG02012) to ZY; the postgraduates innovation special fund project of Jiangxi province (YC2022—B051) and a grant from the Talent Development project of the Affiliated Eye Hospital of Nanchang University (No.2022X05) and to KL. The funders had no role in the study design, data collection, data analysis, interpretation, or writing of the report.