TMEM132D and VIPR2 Polymorphisms as Genetic Risk Loci for Retinal Detachment: A Genome-Wide Association Study and Polygenic Risk Score Analysis

Hao Kai Chuang, Ai Ru Hsieh, Tien Yap Ang, Szu Wen Chen, Yi Ping Yang, Hung Juei Huang, Shih Hwa Chiou, Tai Chi Lin, Shih Jen Chen, Chih Chien Hsu, De Kuang Hwang*

*此作品的通信作者

研究成果: Article同行評審

摘要

PURPOSE. Retinal detachment (RD) is a sight-threatening ocular disease caused by separation of the neurosensory retina from the underlying retinal pigment epithelium layer. Its genetic basis is unclear because of a limited amount of data. In this study, we aimed to identify genetic risk loci associated with RD in participants without diabetes mellitus and to construct a polygenic risk score (PRS) to predict the risk of RD. METHODS. A genome-wide association study was conducted using data from the Taiwan Biobank to identify RD risk loci. A total of 1533 RD cases and 106,270 controls were recruited, all of whom were Han Chinese. Replication studies were performed using data from the UK Biobank and Biobank Japan. To construct the PRS, a traditional clumping and thresholding method was performed and validated by fivefold cross-validation. RESULTS. Two novel loci with significant associations were identified. These two genes were TMEM132D (lead single nucleotide polymorphism [SNP]: rs264498, adjusted-P = 7.18 × 10−9) and VIPR2 (lead SNP: rs3812305, adjusted-P = 8.38 × 10−9). The developed PRS was effective in discriminating individuals at high risk of RD with a dose-response relationship. The quartile with the highest risk had an odds ratio of 1244.748 compared to the lowest risk group (95% confidence interval, 175.174–8844.892). CONCLUSIONS. TMEM132D and VIPR2 polymorphisms are genetic candidates linked to RD in Han Chinese populations. Our proposed PRS was effective at discriminating high-risk from low-risk individuals.

原文English
文章編號17
期刊Investigative Ophthalmology and Visual Science
64
發行號12
DOIs
出版狀態Published - 9月 2023

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