. 2018 Feb 15;8(1):3124.

doi: 10.1038/s41598-018-20435-9.

Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Puya Gharahkhani¹, Kathryn P Burdon², Jessica N Cooke Bailey³, Alex W Hewitt², Matthew H Law⁴, Louis R Pasquale^{5

6}, Jae H Kang⁶, Jonathan L Haines³, Emmanuelle Souzeau⁷, Tiger Zhou⁷, Owen M Siggs⁷, John Landers⁷, Mona Awadalla⁷, Shiwani Sharma⁷, Richard A Mills⁷, Bronwyn Ridge⁷, David Lynn⁸, Robert Casson⁹, Stuart L Graham¹⁰, Ivan Goldberg¹¹, Andrew White^{11

12}, Paul R Healey^{11

12}, John Grigg¹¹, Mitchell Lawlor¹¹, Paul Mitchell¹², Jonathan Ruddle¹³, Michael Coote¹³, Mark Walland¹³, Stephen Best¹⁴, Andrea Vincent¹⁴, Jesse Gale¹⁵, Graham RadfordSmith^{4

16}, David C Whiteman⁴, Grant W Montgomery^{4

17}, Nicholas G Martin⁴, David A Mackey^{2

18}, Janey L Wiggs⁵, Stuart MacGregor⁴, Jamie E Craig¹⁹; NEIGHBORHOOD consortium

Collaborators, Affiliations

Collaborators

Affiliations

¹ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Puya.Gharahkhani@qimrberghofer.edu.au.
² University of Tasmania, Hobart, Tasmania, Australia.
³ Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁴ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁵ Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
⁶ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁷ Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
⁸ South Australian Health & Medical Research Institute, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
⁹ South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
¹⁰ Ophthalmology and Vision Science, Macquarie University, Sydney, New South Wales, Australia.
¹¹ Department of Ophthalmology, University of Sydney, Sydney, Australia.
¹² Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
¹³ Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
¹⁴ Department of Ophthalmology, University of Auckland, Auckland, New Zealand.
¹⁵ Department of Ophthalmology, University of Otago, Dunedin, Otago, New Zealand.
¹⁶ School of Medicine, University of Queensland, Herston Campus, Brisbane, QLD, Australia.
¹⁷ Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
¹⁸ Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
¹⁹ Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. jamie.craig@flinders.edu.au.

PMID: 29449654
PMCID: PMC5814451
DOI: 10.1038/s41598-018-20435-9

Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Puya Gharahkhani et al. Sci Rep. 2018.

. 2018 Feb 15;8(1):3124.

doi: 10.1038/s41598-018-20435-9.

Authors

Collaborators

Affiliations

¹ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. Puya.Gharahkhani@qimrberghofer.edu.au.
² University of Tasmania, Hobart, Tasmania, Australia.
³ Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁴ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
⁵ Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
⁶ Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁷ Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia.
⁸ South Australian Health & Medical Research Institute, School of Medicine, Flinders University, Adelaide, South Australia, Australia.
⁹ South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
¹⁰ Ophthalmology and Vision Science, Macquarie University, Sydney, New South Wales, Australia.
¹¹ Department of Ophthalmology, University of Sydney, Sydney, Australia.
¹² Centre for Vision Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW, Australia.
¹³ Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia.
¹⁴ Department of Ophthalmology, University of Auckland, Auckland, New Zealand.
¹⁵ Department of Ophthalmology, University of Otago, Dunedin, Otago, New Zealand.
¹⁶ School of Medicine, University of Queensland, Herston Campus, Brisbane, QLD, Australia.
¹⁷ Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
¹⁸ Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia.
¹⁹ Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. jamie.craig@flinders.edu.au.

PMID: 29449654
PMCID: PMC5814451
DOI: 10.1038/s41598-018-20435-9

Abstract

Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - "response to fluid shear stress" and "abnormal retina morphology" - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

**Figure 1**
Regional plots for the new risk loci identified in single variant analyses in this study. The most significantly associated SNPs in each region are marked as solid purple diamonds. Pairwise correlations (LD r²) between the top SNP and the other SNPs in a 400 kb flanking region are illustrated by different colours. Blue spikes show estimated recombination rates. (a) rs72815193 on chromosome 10 near *MYOF*, *CYP26A1*, and *CYP26C* (the most significant results were obtained in combined OAG and VCDR analysis conducted in combined Asians and European ancestry). (b) rs56962872 on chromosome 3 within *LOC253573* (*LINC02052)*, near *CRYGS* and *TBCCD1* (the most significant results were obtained in combined OAG and VCDR analysis conducted in European ancestry). (c) rs6478746 on chromosome nine near *LMX1B* (the most significant results were obtained in combined OAG and CA in European ancestry). (d) rs9530458 on chromosome 13 within *LMO7* (combined OAG data from ANZRAG and NEIGHBORHOOD). cM = centimorgan.

See this image and copyright information in PMC

References

1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol. 2006;90:262–267. doi: 10.1136/bjo.2005.081224. - DOI - PMC - PubMed
1. Casson RJ, Chidlow G, Wood JP, Crowston JG, Goldberg I. Definition of glaucoma: clinical and experimental concepts. Clin Exp Ophthalmol. 2012;40:341–349. doi: 10.1111/j.1442-9071.2012.02773.x. - DOI - PubMed
1. Wolfs RC, et al. Genetic risk of primary open-angle glaucoma. Population-based familial aggregation study. Arch Ophthalmol. 1998;116:1640–1645. doi: 10.1001/archopht.116.12.1640. - DOI - PubMed
1. Thorleifsson G, et al. Common variants near CAV1 and CAV2 are associated with primary open-angle glaucoma. Nat Genet. 2010;42:906–909. doi: 10.1038/ng.661. - DOI - PMC - PubMed
1. Burdon KP, et al. Genome-wide association study identifies susceptibility loci for open angle glaucoma at TMCO1 and CDKN2B-AS1. Nat Genet. 2011;43:574–578. doi: 10.1038/ng.824. - DOI - PubMed

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- The Lens - Patent Citations Database
- scite Smart Citations
Research Materials
- NCI CPTC Antibody Characterization Program
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Collaborators

Affiliations

Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Research Materials

Miscellaneous