Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: A multi-cohort analysis

Hugues Aschard, Jae H. Kang, Adriana I. Iglesias, Pirro Hysi, Jessica N. Cooke Bailey, Anthony P. Khawaja, R. Rand Allingham, Allison Ashley-Koch, Richard K. Lee, Sayoko E. Moroi, Murray H. Brilliant, Gadi Wollstein, Joel S. Schuman, John H. Fingert, Donald L. Budenz, Tony Realini, Terry Gaasterland, William K. Scott, Kuldev Singh, Arthur J. SitRobert P. Igo, Yeunjoo E. Song, Lisa Hark, Robert Ritch, Douglas J. Rhee, Vikas Gulati, Shane Haven, Douglas Vollrath, Donald J. Zack, Felipe Medeiros, Robert N. Weinreb, Ching Yu Cheng, Daniel I. Chasman, William G. Christen, Margaret A. Pericak-Vance, Yutao Liu, Peter Kraft, Julia E. Richards, Bernard A. Rosner, Michael A. Hauser, Caroline C.W. Klaver, Cornelia M. Vanduijn, Jonathan Haines, Janey L. Wiggs, Louis R. Pasquale

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1261-1267
Number of pages7
JournalEuropean Journal of Human Genetics
Volume25
Issue number11
DOIs
StatePublished - Nov 1 2017

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Intraocular Pressure
Cohort Studies
Blood Pressure
Genome
Linkage Disequilibrium
Primary Open Angle Glaucoma
Glaucoma
National Eye Institute (U.S.)
Optic Nerve Diseases
Medical Genetics
Epidemiologic Studies
Odds Ratio
Databases
Confidence Intervals

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Aschard, H., Kang, J. H., Iglesias, A. I., Hysi, P., Cooke Bailey, J. N., Khawaja, A. P., ... Pasquale, L. R. (2017). Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: A multi-cohort analysis. European Journal of Human Genetics, 25(11), 1261-1267. https://doi.org/10.1038/ejhg.2017.136

Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma : A multi-cohort analysis. / 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.

In: European Journal of Human Genetics, Vol. 25, No. 11, 01.11.2017, p. 1261-1267.

Research output: Contribution to journalArticle

Aschard, H, Kang, JH, Iglesias, AI, Hysi, P, Cooke Bailey, JN, Khawaja, AP, Allingham, RR, Ashley-Koch, A, Lee, RK, Moroi, SE, Brilliant, MH, Wollstein, G, Schuman, JS, Fingert, JH, Budenz, DL, Realini, T, Gaasterland, T, Scott, WK, Singh, K, Sit, AJ, Igo, RP, Song, YE, Hark, L, Ritch, R, Rhee, DJ, Gulati, V, Haven, S, Vollrath, D, Zack, DJ, Medeiros, F, Weinreb, RN, Cheng, CY, Chasman, DI, Christen, WG, Pericak-Vance, MA, Liu, Y, Kraft, P, Richards, JE, Rosner, BA, Hauser, MA, Klaver, CCW, Vanduijn, CM, Haines, J, Wiggs, JL & Pasquale, LR 2017, 'Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma: A multi-cohort analysis', European Journal of Human Genetics, vol. 25, no. 11, pp. 1261-1267. https://doi.org/10.1038/ejhg.2017.136
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. / Genetic correlations between intraocular pressure, blood pressure and primary open-angle glaucoma : A multi-cohort analysis. In: European Journal of Human Genetics. 2017 ; Vol. 25, No. 11. pp. 1261-1267.
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abstract = "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 {\^a} 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 {\^a} 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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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.

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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