Differences in the Genetic Susceptibility to Age-Related Macular Degeneration Clinical Subtypes.
Differences in the Genetic Susceptibility to Age-Related Macular Degeneration Clinical Subtypes.
复制标题
年龄相关性黄斑变性临床亚型的遗传易感性差异。
DOI：
10.1167/iovs.15-16533
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发表时间：
2015
影响因子：
4.4
通讯作者：
Jorgenson,Eric
中科院分区：
文献类型：
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作者：
Shen,Ling;Hoffmann,ThomasJ;Melles,RonaldB;Sakoda,LoriC;Kvale,MarkN;Banda,Yambazi;Schaefer,Catherine;Risch,Neil;Jorgenson,Eric
目的：我们比较了年龄相关性黄斑变性 (AMD) 亚型的 AMD 风险变异的影响、其预测能力和遗传力。方法：在截至 2013 年 6 月年龄至少 65 岁的活跃非西班牙裔白人北加州 Kaiser Permanente 成员中估计 AMD 患病率。遗传分析包括从电子健康记录 (EHR) 确定的 5,170 例 AMD 病例，其中包括 1,239 例脉络膜病变患者新生血管形成 (CNV) 病例和 1,060 例无 CNV 的非渗出性 AMD 病例，以及来自 Kaiser Permanente 成人健康和衰老遗传流行病学研究 (GERA) 队列的 23,130 名非西班牙裔白人血统对照。估算基于 1000 基因组计划参考小组。 结果：由于常见常染色体单核苷酸多态性 (SNP) 导致的狭义遗传力，总体 AMD 为 0.37，未明确的 AMD 为 0.19，非渗出性 AMD 为 0.20，CNV 为 0.60。对于先前报告的 19 个 AMD 风险位点，总体 AMD 的受试者工作特征 (ROC) 曲线下面积为 0.675，未明确的 AMD 为 0.640，非渗出性 AMD 为 0.678，CNV 为 0.766。 19 个 SNP 中的 18 个对 AMD 风险的个体影响与之前报道的方向一致，包括 APOE ε4 等位基因的保护作用。相反，ε2 等位基因携带者的 AMD 风险显着增加。结论：这些发现为许多先前确定的 AMD 风险位点提供了独立证实，并支持遗传因素在 CNV 发展中可能发挥更大的作用。已建立关联的复制验证了 EHR 在眼科特征遗传研究中的使用。
Purpose: We compared across age-related macular degeneration (AMD) subtypes the effect of AMD risk variants, their predictive power, and heritability.Methods: The prevalence of AMD was estimated among active non-Hispanic white Kaiser Permanente Northern California members who were at least 65 years of age as of June 2013. The genetic analysis included 5,170 overall AMD cases ascertained from electronic health records (EHR), including 1,239 choroidal neovascularization (CNV) cases and 1,060 nonexudative AMD cases without CNV, and 23,130 controls of non-Hispanic white ancestry from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Imputation was based on the 1000 Genomes Project reference panel.Results: The narrow-sense heritability due to common autosomal single nucleotide polymorphisms (SNPs) was 0.37 for overall AMD, 0.19 for AMD unspecified, 0.20 for nonexudative AMD, and 0.60 for CNV. For the 19 previously reported AMD risk loci, the area under the receiver operating characteristic (ROC) curve was 0.675 for overall AMD, 0.640 for AMD unspecified, 0.678 for nonexudative AMD, and 0.766 for CNV. The individual effects on the risk of AMD for 18 of the 19 SNPs were in a consistent direction with those previously reported, including a protective effect of the APOE ε4 allele. Conversely, the risk of AMD was significantly increased in carriers of the ε2 allele.Conclusions: These findings provide an independent confirmation of many of the previously identified AMD risk loci, and support a potentially greater role of genetic factors in the development of CNV. The replication of established associations validates the use of EHR in genetic studies of ophthalmologic traits.