TY - JOUR
T1 - Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma
T2 - A multi-cohort analysis
AU - Aschard, Hugues
AU - Kang, Jae H.
AU - Iglesias, Adriana I.
AU - Hysi, Pirro
AU - Cooke Bailey, Jessica N.
AU - Khawaja, Anthony P.
AU - Allingham, R. Rand
AU - Ashley-Koch, Allison
AU - Lee, Richard K.
AU - Moroi, Sayoko E.
AU - Brilliant, Murray H.
AU - Wollstein, Gadi
AU - Schuman, Joel S.
AU - Fingert, John H.
AU - Budenz, Donald L.
AU - Realini, Tony
AU - Gaasterland, Terry
AU - Scott, William K.
AU - Singh, Kuldev
AU - Sit, Arthur J.
AU - Igo, Robert P.
AU - Song, Yeunjoo E.
AU - Hark, Lisa
AU - Ritch, Robert
AU - Rhee, Douglas J.
AU - Gulati, Vikas
AU - Haven, Shane
AU - Vollrath, Douglas
AU - Zack, Donald J.
AU - Medeiros, Felipe
AU - Weinreb, Robert N.
AU - Cheng, Ching Yu
AU - Chasman, Daniel I.
AU - Christen, William G.
AU - Pericak-Vance, Margaret A.
AU - Liu, Yutao
AU - Kraft, Peter
AU - Richards, Julia E.
AU - Rosner, Bernard A.
AU - Hauser, Michael A.
AU - Klaver, Caroline C.W.
AU - Vanduijn, Cornelia M.
AU - Haines, Jonathan
AU - Wiggs, Janey L.
AU - Pasquale, Louis R.
N1 - Publisher Copyright:
© 2017 The Author(s).
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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 â 27) 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 â 5); 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.
AB - 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 â 27) 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 â 5); 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.
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U2 - 10.1038/ejhg.2017.136
DO - 10.1038/ejhg.2017.136
M3 - Article
C2 - 28853718
AN - SCOPUS:85031314948
SN - 1018-4813
VL - 25
SP - 1261
EP - 1267
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 11
ER -