A Genome‑Wide Association Study for Susceptibility to Axial Length in Highly Myopic Eyes  

作　　者：Qiang Lu Yu Du Ye Zhang Yuxi Chen Hao Li Wenwen He Yating Tang Zhennan Zhao Yinglei Zhang Jihong Wu Xiangjia Zhu Yi Lu 

机构地区：[1]Department of Ophthalmology,Eye and Ear,Nose,and Throat Hospital,Fudan University,83 Fenyang Road,Shanghai 200031,China [2]Eye Institute,Eye and Ear,Nose,and Throat Hospital of Fudan University,Shanghai 200031,China [3]Key Laboratory of Myopia,Ministry of Health,Shanghai 200031,China [4]Shanghai Key Laboratory of Visual Impairment and Restoration,Shanghai 200031,China [5]State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032,China

出　　处：《Phenomics》2023年第3期255-267,共13页表型组学（英文）

基　　金：Funding was provided by the National Natural Science Foundation of China,82122017:Xiangjia Zhu,81970780:Yi Lu,81870642:Xiangjia Zhu,81670835:Yi Lu;Science and Technology Innovation Plan of Shanghai Science and Technology Commission,19441900700:Xiangjia Zhu,21S31904900:Xiangjia Zhu;Shanghai Hospital Development Center,SHDC12019X08:Xiangjia Zhu;Shanghai Shenkang Hospital Development Center,SHDC2020CR4078:Xiangjia Zhu;Double-E Plan of Eye&ENT Hospital,SYA202006:Xiangjia Zhu;Shanghai Municipal Key Clinical Specialty Program,shslczdzk01901:Xiangjia Zhu.

摘　　要：High myopia has long been highly prevalent worldwide with a largely yet unexplained genetic contribution.To identify novel susceptibility genes for axial length(AL)in highly myopic eyes,a genome-wide association study(GWAS)was performed using the genomic dataset of 350 deep whole-genome sequencing data from highly myopic patients.Top single nucleotide polymorphisms(SNPs)were functionally annotated.Immunofluorescence staining,quantitative polymerase chain reaction,and western blot were performed using neural retina of form-deprived myopic mice.Enrichment analyses were further performed.We identified the four top SNPs and found that ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16(ADAMTS16)and Phosphatidylinositol Glycan Anchor Biosynthesis Class Z(PIGZ)had the potential of clinical signifi-cance.Animal experiments confirmed that PIGZ expression could be observed and showed higher expression level in form-deprived mice,especially in the ganglion cell layer.The messenger RNA(mRNA)levels of both ADAMTS16 and PIGZ were significantly higher in the neural retina of form-deprived eyes(p=0.005 and 0.007 respectively),and both proteins showed significantly upregulated expression in the neural retina of deprived eyes(p=0.004 and 0.042,respectively).Enrichment analysis revealed a significant role of cellular adhesion and signal transduction in AL,and also several AL-related pathways including circadian entrainment and inflammatory mediator regulation of transient receptor potential channels were proposed.In conclusion,the current study identified four novel SNPs associated with AL in highly myopic eyes and confirmed that the expression of ADAMTS16 and PIGZ was significantly upregulated in neural retina of deprived eyes.Enrichment analyses provided novel insight into the etiology of high myopia and opened avenues for future research interest.

关 键 词：Axial length High myopia Whole-genome sequencing ADAM Metallopeptidase With Thrombospondin Type 1 Motif 16·Phosphatidylinositol Glycan Anchor Biosynthesis Class Z 

分 类 号：R778.11[医药卫生—眼科]