在非洲祖先的个体中,基因变异与初级开角眼光的关联
, Michael A Hauser1,2,3,4, R Rand Allingham2,3,4
1Department of Medicine, Duke University, Durham, North Carolina.
JAMA
|November 6, 2019
概括
这项全基因组关联研究在APBB2位点发现了一种新的遗传风险变体rs59892895*C,与非洲祖先群体的初级开角青光眼有关. 这一发现可能会改善风险评估,并为这种致盲疾病的治疗策略提供信息.
科学领域:
- 眼科 眼科
- 遗传学
- 基因组学
背景情况:
- 主要开角眼 (POAG) 不成比例地影响非洲血统的个体,患病率和严重程度更高.
- 在非洲祖先群体中对POAG的基因组研究仍然有限,阻碍了对疾病机制和有针对性的干预措施的理解.
研究的目的:
- 在非洲祖先群体中进行全基因组关联研究 (GWAS),以确定与POAG相关的遗传位置.
- 调查已识别的POAG相关位点的潜在致病机制.
主要方法:
- 进行了两阶段的GWAS,包括2320例POAG和2121例对照的发现阶段,随后是6937例POAG和14917例对照的验证阶段.
- 在2003年至2018年期间,从不同国际地点 (非洲,欧洲,美洲) 招募了参与者.
- POAG病例被定义为光眼神经病变和视野缺陷,不包括眼内压力.
主要成果:
- 在GWAS中,在APBB2位点的rs59892895*C变异与POAG之间发现了显著的关联 (P=2×10−8).
- 在独立的队列中成功验证了这种关联 (P<.001),风险等位基因显示累积效应 (OR,1. 19;P=4×10−13).
- 在非洲祖先群体中发现了rs59892895*C等位基因,在欧洲或亚洲祖先群体中发现的频率为<0. 1%.
结论:
- 在APBB2位点的变体显示了跨祖先的POAG差异性关联.
- 在非洲血统中普遍存在的确定的风险基因rss59892895*C可能导致这些人群中的POAG负担较高.
- 进一步的验证和机制研究可能会改善POAG风险分层和新的治疗目标.
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