Aschard Hugues, Kang Jae H, Iglesias Adriana I, Hysi Pirro, Cooke Bailey Jessica N, Khawaja Anthony P, Allingham R Rand, Ashley-Koch Allison, Lee Richard K, Moroi Sayoko E, Brilliant Murray H, Wollstein Gadi, Schuman Joel S, Fingert John H, Budenz Donald L, Realini Tony, Gaasterland Terry, Scott William K, Singh Kuldev, Sit Arthur J, Igo Robert P, Song Yeunjoo E, Hark Lisa, Ritch Robert, Rhee Douglas J, Gulati Vikas, Haven Shane, Vollrath Douglas, Zack Donald J, Medeiros Felipe, Weinreb Robert N, Cheng Ching-Yu, Chasman Daniel I, Christen William G, Pericak-Vance Margaret A, Liu Yutao, Kraft Peter, Richards Julia E, Rosner Bernard A, Hauser Michael A, Klaver Caroline C W, vanDuijn Cornelia M, Haines Jonathan, Wiggs Janey L, Pasquale Louis R
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA.
Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Eur J Hum Genet. 2017 Nov;25(11):1261-1267. doi: 10.1038/ejhg.2017.136. Epub 2017 Aug 30.
Primary open-angle glaucoma (POAG) is the most common chronic optic neuropathy worldwide. Epidemiological studies show a robust positive relation between intraocular pressure (IOP) and POAG and modest positive association between IOP and blood pressure (BP), while the relation between BP and POAG is controversial. The International Glaucoma Genetics Consortium (n=27 558), the International Consortium on Blood Pressure (n=69 395), and the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (n=37 333), represent genome-wide data sets for IOP, BP traits and POAG, respectively. We formed genome-wide significant variant panels for IOP and diastolic BP and found a strong relation with POAG (odds ratio and 95% confidence interval: 1.18 (1.14-1.21), P=1.8 × 10) for the former trait but no association for the latter (P=0.93). Next, we used linkage disequilibrium (LD) score regression, to provide genome-wide estimates of correlation between traits without the need for additional phenotyping. We also compared our genome-wide estimate of heritability between IOP and BP to an estimate based solely on direct measures of these traits in the Erasmus Rucphen Family (ERF; n=2519) study using Sequential Oligogenic Linkage Analysis Routines (SOLAR). LD score regression revealed high genetic correlation between IOP and POAG (48.5%, P=2.1 × 10); however, genetic correlation between IOP and diastolic BP (P=0.86) and between diastolic BP and POAG (P=0.42) were negligible. Using SOLAR in the ERF study, we confirmed the minimal heritability between IOP and diastolic BP (P=0.63). Overall, IOP shares genetic basis with POAG, whereas BP has limited shared genetic correlation with IOP or POAG.
原发性开角型青光眼（POAG）是全球最常见的慢性视神经病变。流行病学研究表明，眼压（IOP）与POAG之间存在强烈的正相关关系，IOP与血压（BP）之间存在适度的正相关关系，而BP与POAG之间的关系存在争议。国际青光眼遗传学联盟（n = 27558）、国际血压联盟（n = 69395）和美国国立眼科研究所青光眼人类遗传学合作遗传性总体操作数据库（n = 37333）分别代表了IOP、BP性状和POAG的全基因组数据集。我们构建了IOP和舒张压的全基因组显著变异面板，发现前者与POAG有很强的相关性（优势比和95%置信区间：1.18（1.14 - 1.21），P = 1.8×10），而后者无相关性（P = 0.93）。接下来，我们使用连锁不平衡（LD）评分回归，在无需额外表型分析的情况下提供性状之间相关性的全基因组估计。我们还将IOP和BP之间的全基因组遗传力估计值与仅基于伊拉斯姆斯鲁芬家族（ERF；n = 2519）研究中这些性状的直接测量值，使用顺序寡基因连锁分析程序（SOLAR）得出的估计值进行了比较。LD评分回归显示IOP与POAG之间存在高度遗传相关性（48.5%，P = 2.1×10）；然而，IOP与舒张压之间（P = 0.86）以及舒张压与POAG之间（P = 0.42）的遗传相关性可忽略不计。在ERF研究中使用SOLAR，我们证实了IOP与舒张压之间的遗传力极小（P = 0.63）。总体而言，IOP与POAG共享遗传基础，而BP与IOP或POAG的共享遗传相关性有限。
