Department of Twin Research and Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, United Kingdom.
King's Genomics Facilities, King's College London, London, United Kingdom.
Ophthalmology. 2017 Apr;124(4):547-553. doi: 10.1016/j.ophtha.2016.11.018. Epub 2016 Dec 27.
Sequence variations in the myocilin (MYOC) gene account for approximately 2% to 4% of glaucoma cases. One particular MYOC mutation, Gln368Stop (dbSNP accession number: rs74315329), is the most common genetic mutation causing glaucoma by increasing intraocular pressure (IOP). The objective of this study was to evaluate the effect of this MYOC mutation on IOP using data from large-scale European population panels (directly sequenced and imputation based).
Cross-sectional, cohort study.
For this study, the penetrance of the variant rs74315329 was estimated in 2 population-based cohorts, the TwinsUK (N = 6092) and the Rotterdam Study (RS) (N =11 189).
Carriers of the risk allele for rs74315329 were identified using whole-genome sequencing and imputation data (based on 1000 Genomes Project and Haplotype Reference Consortium panels). The penetrance of this variant was evaluated using IOP measurements and data on visual field testing/a diagnosis of glaucoma (if available).
The penetrance of the variant rs74315329 was estimated from the percentage of the carriers of the risk allele of the variant who had high IOP (ocular hypertension) or glaucoma.
In our study, the observed penetrance of the variant rs74315329 in relation to increased IOP was 12.5% and 19.4% in the TwinsUK and the RS, respectively. Thus, our study suggests a much lower penetrance for rs74315329 for ocular hypertension (and thus glaucoma), in comparison with that reported previously.
The significance of this finding is that higher numbers of healthy individuals in the population are expected to be carriers of this mutation, which in turn reduces the utility of identifying carriers of this mutation as a screening tool for glaucoma.
肌球蛋白（MYOC）基因中的序列变异约占青光眼病例的 2%至 4%。MYOC 基因的一个特定突变，Gln368Stop（dbSNP 注册号：rs74315329），是通过增加眼内压（IOP）导致青光眼的最常见遗传突变。本研究的目的是使用来自大型欧洲人群面板（直接测序和基于推断）的数据评估该 MYOC 突变对 IOP 的影响。
横断面、队列研究。
在这项研究中，使用基于 TwinsUK（N=6092）和 Rotterdam 研究（RS）（N=11189）的两个基于人群的队列，估计了变体 rs74315329 的外显率。
使用全基因组测序和基于 1000 基因组计划和单倍型参考联盟面板的推断数据，鉴定出 rs74315329 风险等位基因的携带者。使用 IOP 测量值和有关视野测试/青光眼诊断（如果有）的数据来评估该变体的外显率。
从携带该变体风险等位基因的个体中，具有高 IOP（高眼压）或青光眼的比例估计变体 rs74315329 的外显率。
在我们的研究中，变体 rs74315329 与增加的 IOP 相关的观察到的外显率在 TwinsUK 和 RS 中分别为 12.5%和 19.4%。因此，与先前报道相比，我们的研究表明，rs74315329 对高眼压（进而对青光眼）的外显率要低得多。
这一发现的意义在于，人群中预计会有更多的健康个体携带这种突变，这反过来又降低了识别这种突变携带者作为青光眼筛查工具的效用。
