结论:随着额外的青光眼基因的鉴定和分类,多基因风险评分将得到完善,促进早期诊断和治疗。确保基因研究是公平的,在全球范围内预防青光眼失明至关重要。
目的:回顾25年来青光眼遗传学的进展,包括鉴定对疾病有不同贡献的基因和多基因风险评分的发展。
结果:在过去的25年里,青光眼遗传学已经从识别具有孟德尔遗传模式的基因演变而来,如肌蛋白和CYP1B1,以发现与该疾病相关的数百个基因。已经制定了多基因风险评分,主要基于对北欧人口的研究,完善这些分数的努力正在进行中。然而,有一个关于它们对其他种族群体的适用性的问题,尤其是原发性开角型青光眼风险较高的患者,像非洲血统的人。青光眼是高度遗传性的,家族史可用于级联临床筛查计划,但这并不是在所有人群中都可行。因此,使用成熟基因如myocilin的级联基因检测可能有助于改善青光眼的诊断。此外,正在进行的调查试图确定基因中的致病性遗传变异,如myocilin。
结论:对于各种疾病的基因检测的日益普及和对遗传风险信息的早期获取,需要进一步研究以确定何时以及如何对特定的遗传结果采取行动。涉及具有微妙影响的多个基因的多基因风险评分将需要持续改进以提高临床效用。这对于有效解释个体患青光眼和预防失明的风险至关重要。
CONCLUSIONS: As additional glaucoma genes are identified and classified, polygenic risk scores will be refined, facilitating early diagnosis and treatment. Ensuring genetic research is equitable to prevent glaucoma blindness worldwide is crucial.
OBJECTIVE: To review the progress in glaucoma genetics over the past 25 years, including the identification of genes with varying contributions to the disease and the development of polygenic risk scores.
RESULTS: Over the last 2 and a half decades, glaucoma genetics has evolved from identifying genes with Mendelian inheritance patterns, such as myocilin and CYP1B1, to the discovery of hundreds of genes associated with the disease. Polygenic risk scores have been developed, primarily based on research in Northern European populations, and efforts to refine these scores are ongoing. However, there is a question regarding their applicability to other ethnic groups, especially those at higher risk of primary open angle glaucoma, like individuals of African ancestry. Glaucoma is highly heritable and family history can be used for cascade clinical screening programs, but these will not be feasible in all populations. Thus, cascade genetic testing using well-established genes such as myocilin may help improve glaucoma diagnosis. In addition, ongoing investigations seek to identify pathogenic genetic variants within genes like myocilin.
CONCLUSIONS: The expanding availability of genetic testing for various diseases and early access to genetic risk information necessitates further research to determine when and how to act on specific genetic results. Polygenic risk scores involving multiple genes with subtle effects will require continuous refinement to improve clinical utility. This is crucial for effectively interpreting an individual\'s risk of developing glaucoma and preventing blindness.