Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
PLoS One. 2019 Aug 15;14(8):e0220143. doi: 10.1371/journal.pone.0220143. eCollection 2019.
To evaluate the roles of known myopia-associated genetic variants for development of myopic macular degeneration (MMD) in individuals with high myopia (HM), using case-control studies from the Consortium of Refractive Error and Myopia (CREAM).
A candidate gene approach tested 50 myopia-associated loci for association with HM and MMD, using meta-analyses of case-control studies comprising subjects of European and Asian ancestry aged 30 to 80 years from 10 studies. Fifty loci with the strongest associations with myopia were chosen from a previous published GWAS study. Highly myopic (spherical equivalent [SE] ≤ -5.0 diopters [D]) cases with MMD (N = 348), and two sets of controls were enrolled: (1) the first set included 16,275 emmetropes (SE ≤ -0.5 D); and (2) second set included 898 highly myopic subjects (SE ≤ -5.0 D) without MMD. MMD was classified based on the International photographic classification for pathologic myopia (META-PM).
In the first analysis, comprising highly myopic cases with MMD (N = 348) versus emmetropic controls without MMD (N = 16,275), two SNPs were significantly associated with high myopia in adults with HM and MMD: (1) rs10824518 (P = 6.20E-07) in KCNMA1, which is highly expressed in human retinal and scleral tissues; and (2) rs524952 (P = 2.32E-16) near GJD2. In the second analysis, comprising highly myopic cases with MMD (N = 348) versus highly myopic controls without MMD (N = 898), none of the SNPs studied reached Bonferroni-corrected significance.
Of the 50 myopia-associated loci, we did not find any variant specifically associated with MMD, but the KCNMA1 and GJD2 loci were significantly associated with HM in highly myopic subjects with MMD, compared to emmetropes.
使用来自近视研究联合会（CREAM）的病例对照研究，评估已知近视相关遗传变异在高度近视（HM）人群中发生近视性黄斑变性（MMD）的作用。
采用候选基因方法，对 50 个与近视相关的基因座进行荟萃分析，这些基因座与来自 10 项研究的年龄在 30 至 80 岁的欧洲和亚洲血统的病例对照研究相关。从之前发表的 GWAS 研究中选择与近视相关性最强的 50 个基因座。招募了高度近视（等效球镜 [SE] ≤-5.0 屈光度 [D]）且患有 MMD（N=348）的病例，以及两组对照：（1）第一组包括 16275 名正视眼（SE≤-0.5 D）；（2）第二组包括 898 名高度近视（SE≤-5.0 D）但无 MMD 的患者。根据国际病理性近视照相分类（META-PM）对 MMD 进行分类。
在第一次分析中，包括患有 MMD 的高度近视病例（N=348）与无 MMD 的正视对照（N=16275），两个 SNP 与患有 HM 和 MMD 的成人高度近视显著相关：（1）KCNMA1 中的 rs10824518（P=6.20E-07），在人类视网膜和巩膜组织中高度表达；（2）GJD2 附近的 rs524952（P=2.32E-16）。在第二次分析中，包括患有 MMD 的高度近视病例（N=348）与无 MMD 的高度近视对照（N=898），所研究的 SNP 均未达到 Bonferroni 校正的显著性。
在 50 个与近视相关的基因座中，我们没有发现任何特定的与 MMD 相关的变异，但与正视眼相比，KCNMA1 和 GJD2 基因座与高度近视且患有 MMD 的患者的 HM 显著相关。
