澳大利亚昆士兰大学Xikun Han等研究人员利用青光眼的多特征分析，确定了新的风险基因座，并能对疾病的易感性和进展进行多基因预测。2020年1月20日，《自然—遗传学》在线发表了这项成果。
研究人员表征了67040个英国生物银行参与者的视神经照片，并使用多特征遗传模型来识别青光眼的风险基因座。青光眼多基因风险评分（PRS）可在未经选择的青光眼病例中进行有效的风险分层，并修改编码p.Gln368Ter的MYOC变异体外显率，这是最常见的与青光眼相关的肌球蛋白变异体。在未经选择的青光眼人群中，处于PRS最高位的人比处于最低位的人早10年达到绝对的青光眼风险，发展成晚期青光眼的风险增加了15倍（前10％对剩余的90％，优势比=4.20）。PRS能够预测在前瞻性监测早期青光眼病例中的青光眼进展（P=0.004）和晚期疾病的手术干预（P=3.6×10-6）。青光眼PRS将促进针对早期高危人群个性化治疗方法的开发，而对于低危人群则可能进行强度较低的监测和治疗。
据了解，青光眼是一种以进行性视神经变性为特征的疾病，可以通过及时诊断和治疗来预防。
附：英文原文
Title: Multitrait analysis of glaucoma identifies new risk loci and enables polygenic prediction of disease susceptibility and progression
Author: Jamie E. Craig, Xikun Han, Ayub Qassim, Mark Hassall, Jessica N. Cooke Bailey, Tyler G. Kinzy, Anthony P. Khawaja, Jiyuan An, Henry Marshall, Puya Gharahkhani, Robert P. Igo, Stuart L. Graham, Paul R. Healey, Jue-Sheng Ong, Tiger Zhou, Owen Siggs, Matthew H. Law, Emmanuelle Souzeau, Bronwyn Ridge, Pirro G. Hysi, Kathryn P. Burdon, Richard A. Mills, John Landers, Jonathan B. Ruddle, Ashish Agar, Anna Galanopoulos, Andrew J. R. White, Colin E. Willoughby, Nicholas H. Andrew, Stephen Best, Andrea L. Vincent, Ivan Goldberg, Graham Radford-Smith, Nicholas G. Martin, Grant W. Montgomery, Veronique Vitart, Rene Hoehn, Robert Wojciechowski, Jost B. Jonas, Tin Aung, Louis R. Pasquale, Angela Jane Cree, Sobha Sivaprasad, Neeru A. Vallabh, Ananth C. Viswanathan, Francesca Pasutto, Jonathan L. Haines, Caroline C. W. Klaver, Cornelia M. van Duijn, Robert J. Casson, Paul J. Foster, Peng Tee Khaw, Christopher J. Hammond, David A. Mackey, Paul Mitchell, Andrew J. Lotery, Janey L. Wiggs, Alex W. Hewitt, Stuart MacGregor
Issue&Volume: 2020-01-20
Abstract: Glaucoma, a disease characterized by progressive optic nerve degeneration, can be prevented through timely diagnosis and treatment. We characterize optic nerve photographs of 67,040 UK Biobank participants and use a multitrait genetic model to identify risk loci for glaucoma. A glaucoma polygenic risk score (PRS) enables effective risk stratification in unselected glaucoma cases and modifies penetrance of the MYOC variant encoding p.Gln368Ter, the most common glaucoma-associated myocilin variant. In the unselected glaucoma population, individuals in the top PRS decile reach an absolute risk for glaucoma 10 years earlier than the bottom decile and are at 15-fold increased risk of developing advanced glaucoma (top 10% versus remaining 90%, odds ratio=4.20). The PRS predicts glaucoma progression in prospectively monitored, early manifest glaucoma cases (P=0.004) and surgical intervention in advanced disease (P=3.6×106). This glaucoma PRS will facilitate the development of a personalized approach for earlier treatment of high-risk individuals, with less intensive monitoring and treatment being possible for lower-risk groups.
DOI: 10.1038/s41588-019-0556-y
Source: https://www.nature.com/articles/s41588-019-0556-y
Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
