ImportanceEffects of genetic variants on primary angle-closure disease remained uncertain.ObjectiveTo systematically review the associations of common single-nucleotide variants (SNVs) and rare coding variants with primary angle-closure disease, its subtypes (including primary angle-closure glaucoma, primary angle-closure suspect, and primary angle-closure) and progression.Data SourcesEligible studies from PubMed, Embase, and Web of Science were retrieved up to April 3, 2023. SNV information was extracted from eligible reports and 2 genome-wide association studies summary statistics, UK BioBank and FinnGen.Study SelectionStudies providing analyzable genotype or allele data in a case-control design for primary angle-closure disease association and longitudinal case-only design for primary angle-closure disease progression.Data Extraction and SynthesisPRISMA guidelines were used for literature screening and the Newcastle Ottawa Scale for data quality assessment. Pooled effect size with 95% CIs of SNV associations were calculated using fixed- or random-effect models according to I2 statistics.Main Outcomes and MeasuresSNVs reported in 2 or more studies were meta-analyzed to generate pooled odds ratios and P values. Common and rare coding variants from single reports were summarized.ResultsSixty-nine citations were eligible for meta-analysis on overall primary angle-closure disease, involving 206 SNVs in 64 genes or loci. Seventeen SNVs in 15 genes or loci showed associations with primary angle-closure disease, and 15 SNVs in 13 genes or loci showed associations with primary angle-closure glaucoma. Two SNVs, ABCA1 rs2422493 and ZNRF3 rs3178915, were associated only with primary angle-closure disease. Two SNVs, PCMTD1-ST18 rs1015213 and COL11A1 rs3753841, were associated with primary angle-closure suspect, and 1 SNV, MMP9 rs3918249, was associated with primary angle-closure. This systematic review and meta-analysis newly confirmed 7 genes or loci associated with primary angle-closure glaucoma: ATOH7, CALCRL, FBN1, IL6, LOXL1, MMP19, and VAV3. Common and rare coding variants in 16 genes or loci that have been associated with primary angle-closure disease were cataloged. Stratification analysis revealed different primary angle-closure disease–associated genes in different ethnic populations. Only 1 study regarding the genetic association of primary angle-closure glaucoma progression was identified.Conclusions and RelevanceThis study revealed the genetic complexity of primary angle-closure disease, involving common SNVs and rare coding variants in more than 30 genes or loci, with ethnic and phenotypic diversities. Further replication, genotype-phenotype correlation, and pathway analyses are warranted.

中文翻译：

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原发性闭角病的遗传关联

遗传变异对原发性闭角病的影响仍不确定。目的系统评价常见单核苷酸变异（SNV）和罕见编码变异与原发性闭角病及其亚型（包括原发性闭角型青光眼、原发性角闭角病）的关系。 -闭合可疑和初级闭角）和进展。数据来源检索到截至 2023 年 4 月 3 日的 PubMed、Embase 和 Web of Science 的合格研究。SNV 信息从合格报告和 2 个全基因组关联研究汇总统计中提取、UK BioBank 和 FinnGen。研究选择研究在原发性闭角疾病关联的病例对照设计和原发性闭角疾病进展的纵向仅病例设计中提供可分析的基因型或等位基因数据。数据提取和合成PRISMA 指南用于文献筛选和纽卡斯尔渥太华量表进行数据质量评估。根据以下公式，使用固定或随机效应模型计算 SNV 关联的 95% CI 的合并效应大小我2主要结果和测量对 2 项或更多研究中报告的 SNV 进行荟萃分析，以生成汇总比值比和磷价值观。总结了单个报告中常见和罕见的编码变异。结果 69 条引用符合总体原发性闭角病的荟萃分析，涉及 64 个基因或位点的 206 个 SNV。 15 个基因或位点中的 17 个 SNV 显示与原发性闭角型青光眼相关，13 个基因或位点中的 15 个 SNV 显示与原发性闭角型青光眼相关。两个 SNV，ABCA1rs2422493 和ZNRF3rs3178915 仅与原发性闭角疾病相关。两个 SNV，PCMTD1-ST18rs1015213 和科尔11A1rs3753841，与主要闭角嫌疑人相关，以及 1 个 SNV，基质金属蛋白酶9rs3918249，与原发性闭角相关。这项系统回顾和荟萃分析新证实了与原发性闭角型青光眼相关的 7 个基因或基因座：ATOH7,计算机辅助学习,FBN1,白细胞介素6,LOXL1,基质金属蛋白酶19， 和变速AV3。对与原发性闭角病相关的 16 个基因或基因座中常见和罕见的编码变异进行了编目。分层分析揭示了不同种族人群中不同的原发性闭角病相关基因。仅发现了 1 项关于原发性闭角型青光眼进展的遗传关联的研究。结论和相关性这项研究揭示了原发性闭角型青光眼的遗传复杂性，涉及 30 多个基因或位点的常见 SNV 和罕见编码变异，涉及种族和基因组。表型多样性。进一步的复制、基因型-表型相关性和途径分析是必要的。