Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy
Genome-Wide Association Study of Age-Related Macular Degeneration Reveals 2 New Loci Implying Shared Genetic Components with Central Serous Chorioretinopathy
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DOI：
10.1016/j.ophtha.2022.10.034
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发表时间：
2023-03-20
期刊：
影响因子：
13.7
通讯作者：
Kamatani, Yoichiro
中科院分区：
文献类型：
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作者：
Akiyama, Masato;Miyake, Masahiro;Kamatani, Yoichiro
目的：调查日本人群中年龄相关性黄斑变性 (AMD) 的遗传结构。设计：全基因组关联研究（GWAS）。参与者：来自日本人群的 37772 名 AMD 患者和 16770 名对照参与者被纳入关联分析。方法：我们使用针对日本人群指定的基因型插补参考面板（n = 3541）对 2 个独立的 GWAS 进行了荟萃分析，其中包括总共 2663 名 AMD 患者和 9471 名对照参与者。使用一组独立的 1109 名 AMD 患者和 7299 名对照参与者进行了重复研究。主要结果指标：遗传变异与 AMD 的关联。结果：2 个 GWAS 的荟萃分析确定了 6 个与 AMD 显着相关的位点 (P < 5.0 x 10-8)。在这些位点中，4 个已知与 AMD 相关（CFH、C2/FB、TNFRSF10A 和 ARMS2），2 个是新位点（靠近 WBP1L 的 rs4147157 和靠近 GATA5 的 rs76228488）。新发现的关联在重复研究中得到证实（P < 0.01）。对所有数据集进行荟萃分析后，我们观察到这些位点之间存在很强的关联性（对于 rs4147157 和 rs76228488 的荟萃分析分别为 P = 1.88 x 10-12 和 P = 1.35 x 10-9）。当我们在日本人群中进行的中心性浆液性脉络膜视网膜病变 (CSC) GWAS 中查找相关性时，发现两个基因座均与 CSC 显着相关（rs4147157 和 rs76228488 分别为 P = 4.86 x 10-3 和 P = 4.28 x 10-3）。我们对这些基因座进行了遗传共定位分析，并估计 WBP1L 和 GATA5 之间 AMD 和 CSC 之间共享因果变异的后验概率分别为 0.39 和 0.60。遗传相关分析侧重于流行病学建议的临床危险因素，涉及 AMD 和戒烟之间共有的多基因结构（rg [遗传相关性测量] = -0.33；P = 0.01；错误发现率，0.099）。参考。美国眼科学会 2023 年眼科；130:361-372 (c) 2022
Purpose: To investigate the genetic architecture of age-related macular degeneration (AMD) in a Japanese population. Design: Genome-wide association study (GWAS). Participants: Three thousand seven hundred seventy-two patients with AMD and 16 770 control participants from the Japanese population were enrolled in the association analyses. Methods: We conducted a meta-analysis of 2 independent GWASs that included a total of 2663 patients with AMD and 9471 control participants using the imputation reference panel for genotype imputation specified for the Japanese population (n = 3541). A replication study was performed using an independent set of 1109 patients with AMD and 7299 control participants. Main Outcome Measures: Associations of genetic variants with AMD. Results: A meta-analysis of the 2 GWASs identified 6 loci significantly associated with AMD (P < 5.0 x 10-8). Of these loci, 4 were known to be associated with AMD (CFH, C2/FB, TNFRSF10A, and ARMS2), and 2 were novel (rs4147157 near WBP1L and rs76228488 near GATA5). The newly identified associations were confirmed in a replication study (P < 0.01). After the meta-analysis of all datasets, we observed strong associations in these loci (P = 1.88 x 10-12 and P = 1.35 x 10-9 for meta-analysis for rs4147157 and rs76228488, respectively). When we looked up the associations in the reported central serous chorioretinopathy (CSC) GWAS conducted in the Japanese population, both loci were associated significantly with CSC (P = 4.86 x 10-3 and P = 4.28 x 10-3 for rs4147157 and rs76228488, respectively). We performed a genetic colocalization analysis for these loci and estimated that the posterior probabilities of shared causal variants between AMD and CSC were 0.39 and 0.60 for WBP1L and GATA5, respectively. Genetic correlation analysis focusing on the epidemiologically suggested clinical risk factors implicated shared polygenic architecture between AMD and smoking cessation (rg [the measure of genetic correlation] = -0.33; P = 0.01; false discovery rate, 0.099). references. Ophthalmology 2023;130:361-372 (c) 2022 by the American Academy of Ophthalmology