Determining possible shared genetic architecture between myopia and primary open-angle glaucoma

International Glaucoma Genetics Consortium; The CREAM Consortium

doi:10.1167/iovs.18-26231

Determining possible shared genetic architecture between myopia and primary open-angle glaucoma

International Glaucoma Genetics Consortium, The CREAM Consortium

College of Medicine and Public Health

Research output: Contribution to journal › Article › peer-review

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Abstract

PURPOSE. To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). METHODS. We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23 and Me. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. RESULTS. We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup–disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 3 10) and a significant association between PRS for myopia and disc area (P = 1.59 3 10). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10), supporting the findings of the PRS approach. CONCLUSIONS. Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology.

Original language	English
Pages (from-to)	3142-3149
Number of pages	8
Journal	Investigative Ophthalmology and Visual Science
Volume	60
Issue number	8
DOIs	https://doi.org/10.1167/iovs.18-26231
Publication status	Published - 1 Jul 2019

Bibliographical note

(CC_BY_NC_ND 4.0) Distributed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. NonCommercial — You may not use the material for commercial purposes. NoDerivatives — If you remix, transform, or build upon the material, you may not distribute the modified material.

Keywords

error
genetic overlap
polygenic risk score
primary open-angle glaucoma

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Cite this

@article{36ba5b8cf12e4c25a4d2932673c797dd,

title = "Determining possible shared genetic architecture between myopia and primary open-angle glaucoma",

abstract = "PURPOSE. To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). METHODS. We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23 and Me. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. RESULTS. We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup–disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 3 10) and a significant association between PRS for myopia and disc area (P = 1.59 3 10). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10), supporting the findings of the PRS approach. CONCLUSIONS. Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology.",

keywords = "error, genetic overlap, polygenic risk score, primary open-angle glaucoma",

author = "Iglesias, {Adriana I.} and Ong, {Jue Sheng} and Khawaja, {Anthony P.} and Puya Gharahkhani and Tedja, {Milly S.} and Verhoeven, {Virginie J.M.} and Bonnemaijer, {Pieter W.M.} and Wolfs, {Roger C.W.} and Young, {Terri L.} and Jansonius, {Nomdo M.} and Craig, {Jamie E.} and Dwight Stambolian and {van Duijn}, {Cornelia M.} and Stuart MacGregor and Klaver, {Caroline C.W.} and {International Glaucoma Genetics Consortium} and {The CREAM Consortium}",

note = "(CC_BY_NC_ND 4.0) Distributed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. NonCommercial — You may not use the material for commercial purposes. NoDerivatives — If you remix, transform, or build upon the material, you may not distribute the modified material. ",

year = "2019",

month = jul,

day = "1",

doi = "10.1167/iovs.18-26231",

language = "English",

volume = "60",

pages = "3142--3149",

journal = "Investigative Ophthalmology and Visual Science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology Inc.",

number = "8",

}

TY - JOUR

T1 - Determining possible shared genetic architecture between myopia and primary open-angle glaucoma

AU - Iglesias, Adriana I.

AU - Ong, Jue Sheng

AU - Khawaja, Anthony P.

AU - Gharahkhani, Puya

AU - Tedja, Milly S.

AU - Verhoeven, Virginie J.M.

AU - Bonnemaijer, Pieter W.M.

AU - Wolfs, Roger C.W.

AU - Young, Terri L.

AU - Jansonius, Nomdo M.

AU - Craig, Jamie E.

AU - Stambolian, Dwight

AU - van Duijn, Cornelia M.

AU - MacGregor, Stuart

AU - Klaver, Caroline C.W.

AU - International Glaucoma Genetics Consortium

AU - The CREAM Consortium

N1 - (CC_BY_NC_ND 4.0) Distributed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use. NonCommercial — You may not use the material for commercial purposes. NoDerivatives — If you remix, transform, or build upon the material, you may not distribute the modified material.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - PURPOSE. To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). METHODS. We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23 and Me. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. RESULTS. We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup–disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 3 10) and a significant association between PRS for myopia and disc area (P = 1.59 3 10). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10), supporting the findings of the PRS approach. CONCLUSIONS. Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology.

AB - PURPOSE. To determine genetic correlations between common myopia and primary open-angle glaucoma (POAG). METHODS. We tested the association of myopia polygenic risk scores (PRSs) with POAG and POAG endophenotypes using two studies: the Australian & New Zealand Registry of Advanced Glaucoma (ANZRAG) study comprising 798 POAG cases with 1992 controls, and the Rotterdam Study (RS), a population-based study with 11,097 participants, in which intraocular pressure (IOP) and optic disc parameter measurements were catalogued. PRSs were derived from genome-wide association study meta-analyses conducted by the Consortium for Refractive Error and Myopia (CREAM) and 23 and Me. In total, 12 PRSs were constructed and tested. Further, we explored the genetic correlation between myopia, POAG, and POAG endophenotypes by using the linkage disequilibrium score regression (LDSC) method. RESULTS. We did not find significant evidence for an association between PRS of myopia with POAG (P = 0.81), IOP (P = 0.07), vertical cup–disc ratio (P = 0.42), or cup area (P = 0.25). We observed a nominal association with retinal nerve fiber layer (P = 7.7 3 10) and a significant association between PRS for myopia and disc area (P = 1.59 3 10). Using the LDSC method, we found a genetic correlation only between myopia and disc area (genetic correlation [RhoG] = -0.12, P = 1.8 × 10), supporting the findings of the PRS approach. CONCLUSIONS. Using two complementary approaches we found no evidence to support a genetic overlap between myopia and POAG; our results suggest that the comorbidity of these diseases is not influenced by common variants. The association between myopia and optic disc size is well known and validates this methodology.

KW - error

KW - genetic overlap

KW - polygenic risk score

KW - primary open-angle glaucoma

UR - http://www.scopus.com/inward/record.url?scp=85071632236&partnerID=8YFLogxK

U2 - 10.1167/iovs.18-26231

DO - 10.1167/iovs.18-26231

M3 - Article

C2 - 31323684

AN - SCOPUS:85071632236

SN - 0146-0404

VL - 60

SP - 3142

EP - 3149

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

IS - 8

ER -

Determining possible shared genetic architecture between myopia and primary open-angle glaucoma

Abstract

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Keywords

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