QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Division of Research, Kaiser Permanente Northern California (KPNC), Oakland, CA, USA.
Nat Commun. 2021 Feb 24;12(1):1258. doi: 10.1038/s41467-020-20851-4.
Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.
原发性开角型青光眼（POAG）是一种具有遗传性的常见致盲眼病，在全球范围内普遍存在。为了确定风险基因座，我们对总共 34179 例病例和 349321 例对照进行了大规模的多民族全基因组关联研究的荟萃分析，确定了 44 个以前未报道的风险基因座，并确认了 83 个先前已知的基因座。大多数基因座在欧洲、亚洲和非洲血统中具有广泛一致的影响。跨血统数据可改善多个基因座的因果变异的精细映射。多种遗传证据的综合分析支持所确定的 POAG 风险基因座的功能相关性，并突出了几个基因对 POAG 发病机制的潜在贡献，包括 SVEP1、RERE、VCAM1、ZNF638、CLIC5、SLC2A12、YAP1、MXRA5 和 SMAD6。几种针对 POAG 风险基因的药物化合物可能是潜在的青光眼治疗候选药物。
