Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium
Genetic variants linked to myopic macular degeneration in persons with high myopia: CREAM Consortium
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DOI：
10.1371/journal.pone.0220143
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发表时间：
2019-08
期刊：
影响因子：
3.7
通讯作者：
Yee-Ling Wong;P. Hysi;G. Cheung;M. Tedja;Q. Hoang;S. Tompson;Kristina N. Whisenhunt;V. Verhoeven;Wanting Zhao;Moritz Hess;C. Wong;A. Kifley;Yoshikatsu Hosoda;A. Haarman;Susanne Hopf;P. Laspas;S. Sensaki;X. Sim;M. Miyake;A. Tsujikawa;E. Lamoureux;K. Ohno-Matsui;S. Nickels;P. Mitchell;T. Wong;Jie-Jin Wang;C. Hammond;V. Barathi;Ching-Yu Cheng;K. Yamashiro;T. Young;C. Klaver;S. Saw
中科院分区：
文献类型：
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作者：
Yee-Ling Wong;P. Hysi;G. Cheung;M. Tedja;Q. Hoang;S. Tompson;Kristina N. Whisenhunt;V. Verhoeven;Wanting Zhao;Moritz Hess;C. Wong;A. Kifley;Yoshikatsu Hosoda;A. Haarman;Susanne Hopf;P. Laspas;S. Sensaki;X. Sim;M. Miyake;A. Tsujikawa;E. Lamoureux;K. Ohno-Matsui;S. Nickels;P. Mitchell;T. Wong;Jie-Jin Wang;C. Hammond;V. Barathi;Ching-Yu Cheng;K. Yamashiro;T. Young;C. Klaver;S. Saw
目的利用屈光不正与近视联盟（CREAM）的病例对照研究，评估已知近视相关基因变异在高度近视（HM）患者近视黄斑变性（MMD）发展中的作用。方法采用候选基因方法检测了50个近视相关基因座与HM和烟雾病的相关性，对10项研究的病例对照研究进行了荟萃分析，这些研究包括年龄在30至80岁之间的欧洲和亚洲受试者。从之前发表的GWAS研究中选择了50个与近视密切相关的基因座。高度近视（球面等效度[SE]≤-5.0屈光度[D]）合并烟雾病患者（N = 348），并纳入两组对照：(1)第一组包括16275名近视患者（SE≤-0.5 D）；(2)第二组纳入898名高度近视受试者（SE≤-5.0 D），无烟雾病。根据国际病理性近视摄影分类（META-PM）对烟雾病进行分类。结果在第一个分析中，包括重度烟雾病患者（N = 348）和非烟雾病患者（N = 16,275）的高度近视对照，两个snp与重度烟雾病患者的高度近视显著相关：(1)KCNMA1中rs10824518 (P = 6.20E-07)，在人视网膜和巩膜组织中高度表达；(2) GJD2附近rs524952 （P = 2.32E-16）。在第二项分析中，包括重度近视伴烟雾病的病例（N = 348）和非烟雾病的高度近视对照（N = 898），研究的snp均未达到bonferroni校正的显著性。结论：在50个近视相关基因座中，我们没有发现任何与烟雾病特异性相关的变异，但与烟雾病患者相比，KCNMA1和GJD2基因座与高度近视患者的HM显著相关。
Purpose 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). Methods 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). Results 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. Conclusions 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.