Wiggs Janey L, Pasquale Louis R
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear, Boston, MA 02114, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02114, USA.
Hum Mol Genet. 2017 Aug 1;26(R1):R21-R27. doi: 10.1093/hmg/ddx184.
Genetic and genomic studies, including genome-wide association studies (GWAS) have accelerated the discovery of genes contributing to glaucoma, the leading cause of irreversible blindness world-wide. Glaucoma can occur at all ages, with Mendelian inheritance typical for the rare early onset disease (before age 40) and complex inheritance evident in common adult-onset forms of disease. Recent studies have suggested possible therapeutic targets for some patients with early-onset glaucoma based on the molecular and cellular events caused by MYOC, OPTN and TBK1 mutations. Diagnostic genetic tests using early-onset glaucoma genes are also proving useful for pre-symptomatic disease detection and genetic counseling. Recent GWAS completed for three types of common adult-onset glaucoma have identified novel loci for POAG (primary-open-angle glaucoma) (ABCA1, AFAP1, GMDS, PMM2, TGFBR3, FNDC3B, ARHGEF12, GAS7, FOXC1, ATXN2, TXNRD2); PACG (primary angle-closure glaucoma (EPDR1, CHAT, GLIS3, FERMT2, DPM2-FAM102); and exfoliation syndrome (XFS) glaucoma (CACNA1A). In total sixteen genomic regions have been associated with POAG (including the normal tension glaucoma (NTG) subgroup), 8 with PACG and 2 with XFS. These studies are defining important biological pathways and processes that contribute to disease pathogenesis.
包括全基因组关联研究（GWAS）在内的遗传和基因组研究加速了对导致青光眼的基因的发现，青光眼是全球不可逆失明的主要原因。青光眼可发生于所有年龄段，孟德尔遗传是罕见的早发性疾病（40岁之前）的典型特征，而复杂遗传在常见的成人发病形式的疾病中很明显。最近的研究基于由MYOC、OPTN和TBK1突变引起的分子和细胞事件，为一些早发性青光眼患者提出了可能的治疗靶点。使用早发性青光眼基因的诊断性基因检测也被证明对症状前疾病检测和遗传咨询有用。最近针对三种常见的成人发病型青光眼完成的GWAS已经确定了原发性开角型青光眼（POAG）（ABCA1、AFAP1、GMDS、PMM2、TGFBR3、FNDC3B、ARHGEF12、GAS7、FOXC1、ATXN2、TXNRD2）、原发性闭角型青光眼（PACG）（EPDR1、CHAT、GLIS3、FERMT2、DPM2-FAM102）和剥脱综合征（XFS）青光眼（CACNA1A）的新基因座。总共有16个基因组区域与POAG（包括正常眼压性青光眼（NTG）亚组）相关，8个与PACG相关，2个与XFS相关。这些研究正在确定导致疾病发病机制的重要生物学途径和过程。
