Folkhälsan Research Center, Biomedicum Helsinki, Helsinki, Finland.
Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Helsinki, Finland.
JAMA Ophthalmol. 2021 Jul 1;139(7):762-768. doi: 10.1001/jamaophthalmol.2021.1610.
The c.1102C>T, p.(Gln368Ter) variant in the myocilin (MYOC) gene is a known risk allele for glaucoma. It is the most common MYOC risk variant for glaucoma among individuals of European ancestry, and its prevalence is highest in Finland. Furthermore, exfoliation syndrome has high prevalence in Scandinavia, making the Finnish population ideal to study the association of the variant with different types of glaucoma.
To examine the association and penetrance of MYOC p.(Gln368Ter) (rs74315329) variant with different types of glaucoma in a Finnish population.
DESIGN, SETTING, AND PARTICIPANTS: This genetic association study included individuals of Finnish ancestry in the FinnGen project. The participants were collected from Finnish biobanks, and the disease end points were defined using nationwide registries. The MYOC c.1102C>T variant was either directly genotyped or imputed with microarrays. Recruitment of samples to FinnGen was initiated in 2017, and data analysis was performed between December 2019 and May 2020.
The main outcomes were odds ratios (ORs) and penetrance with different types of glaucoma and in different age groups.
A total of 218 792 individuals were included in this study (mean [SD] age 52.4 [17.5] years; 123 579 women [56.5%]), including 8591 (3.9%) with glaucoma, 3412 (1.6%) with primary open-angle glaucoma, 1515 (0.7%) with exfoliation glaucoma, 892 (0.4%) with normal-tension glaucoma, and 4766 (2.2%) with suspected glaucoma. The minor allele frequency of MYOC p.(Gln368Ter) was 0.28%. Individuals with the heterozygous variant had higher odds of primary open-angle glaucoma (OR, 3.36; 95% CI, 2.55-4.37), overall glaucoma (OR, 2.58; 95% CI, 2.12-3.13), suspected glaucoma (OR, 2.53; 95% CI, 1.93-3.26), exfoliation glaucoma (OR, 2.61; 95% CI, 1.60-4.02), and undergoing glaucoma-related operations (OR, 5.45; 95% CI, 2.95-9.28). The penetrance of heterozygous MYOC p.(Gln368Ter) was 5.2% in individuals with primary open-angle glaucoma, 9.6% in individuals with glaucoma, 5.4% in individuals with suspected glaucoma, and 1.9% in individuals with exfoliation glaucoma. There was no significant association with normal-tension glaucoma (OR, 1.69; 95% CI, 0.72-3.35).
This genetic association study found that the MYOC p.(Gln368Ter) variant was associated with exfoliation glaucoma. The association with normal-tension glaucoma could not be replicated. These findings suggest that MYOC p.(Gln368Ter) was associated with open-angle glaucoma and exfoliation glaucoma in a Finnish population.
Myocilin（MYOC）基因中的 c.1102C>T，p.（Gln368Ter）变体是青光眼的已知风险等位基因。它是欧洲血统个体中最常见的 MYOC 青光眼风险变体，在芬兰其流行率最高。此外，剥脱综合征在斯堪的纳维亚地区高发，这使得芬兰人群成为研究该变体与不同类型青光眼之间关联的理想人群。
在芬兰人群中研究 MYOC p.（Gln368Ter）（rs74315329）变体与不同类型青光眼的关联和外显率。
设计、地点和参与者：这是一项遗传关联研究，纳入了芬兰裔的 FinnGen 项目参与者。参与者来自芬兰生物库，使用全国性登记处来定义疾病终点。直接对 MYOC c.1102C>T 变体进行基因分型或使用微阵列进行推断。FinnGen 于 2017 年开始招募样本，2019 年 12 月至 2020 年 5 月进行数据分析。
主要结果是不同类型青光眼和不同年龄组的比值比（OR）和外显率。
这项研究共纳入了 218792 名个体（平均[标准差]年龄 52.4[17.5]岁；123579 名女性[56.5%]），包括 8591 名（3.9%）青光眼患者、3412 名（1.6%）原发性开角型青光眼患者、1515 名（0.7%）剥脱性青光眼患者、892 名（0.4%）正常眼压性青光眼患者和 4766 名（2.2%）疑似青光眼患者。MYOC p.（Gln368Ter）的次要等位基因频率为 0.28%。携带杂合变体的个体患原发性开角型青光眼（OR，3.36；95%CI，2.55-4.37）、总体青光眼（OR，2.58；95%CI，2.12-3.13）、疑似青光眼（OR，2.53；95%CI，1.93-3.26）、剥脱性青光眼（OR，2.61；95%CI，1.60-4.02）和接受青光眼相关手术（OR，5.45；95%CI，2.95-9.28）的可能性更高。杂合 MYOC p.（Gln368Ter）在原发性开角型青光眼患者中的外显率为 5.2%，在青光眼患者中为 9.6%，在疑似青光眼患者中为 5.4%，在剥脱性青光眼患者中为 1.9%。与正常眼压性青光眼（OR，1.69；95%CI，0.72-3.35）无显著关联。
这项遗传关联研究发现，MYOC p.（Gln368Ter）变体与剥脱性青光眼相关。与正常眼压性青光眼的关联无法复制。这些发现表明，在芬兰人群中，MYOC p.（Gln368Ter）与开角型青光眼和剥脱性青光眼有关。
