Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma

Stuart MacGregor; Jue-Sheng Ong; Jiyuan An; Xikun Han; Tiger Zhou; Owen M Siggs; Matthew H Law; Emmanuelle Souzeau; Shiwani Sharma; David J Lynn; Jonathan Beesley; Bronwyn Sheldrick; Richard A Mills; John Landers; Jonathan B Ruddle; Stuart L Graham; Paul R Healey; Andrew J R White; Robert J Casson; Stephen Best; John R Grigg; Ivan Goldberg; Joseph E Powell; David C Whiteman; Graham L Radford-Smith; Nicholas G Martin; Grant W Montgomery; Kathryn P Burdon; David A Mackey; Puya Gharahkhani; Jamie E Craig; Alex W Hewitt

doi:10.1038/s41588-018-0176-y

Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma

Nat Genet. 2018 Aug;50(8):1067-1071. doi: 10.1038/s41588-018-0176-y. Epub 2018 Jul 27.

Authors

Stuart MacGregor¹, Jue-Sheng Ong², Jiyuan An², Xikun Han², Tiger Zhou³, Owen M Siggs³, Matthew H Law², Emmanuelle Souzeau³, Shiwani Sharma³, David J Lynn^{4

5

6}, Jonathan Beesley², Bronwyn Sheldrick³, Richard A Mills³, John Landers³, Jonathan B Ruddle⁷, Stuart L Graham⁸, Paul R Healey^{9

10}, Andrew J R White⁹, Robert J Casson¹¹, Stephen Best¹², John R Grigg¹⁰, Ivan Goldberg¹⁰, Joseph E Powell^{13

14}, David C Whiteman², Graham L Radford-Smith^{2

15}, Nicholas G Martin², Grant W Montgomery¹⁶, Kathryn P Burdon^{3

17}, David A Mackey^{17

18}, Puya Gharahkhani², Jamie E Craig³, Alex W Hewitt^{7

17}

Affiliations

¹ QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. stuart.macgregor@qimrberghofer.edu.au.
² QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
³ Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
⁴ South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
⁵ EMBL Australia Group, Infection & Immunity Theme, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.
⁶ College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.
⁷ Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia.
⁸ Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
⁹ Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia.
¹⁰ Discipline of Ophthalmology, Faculty of Medicine & Health Sciences, University of Sydney, Sydney Eye Hospital, Sydney, New South Wales, Australia.
¹¹ South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia.
¹² Eye Department, Greenlane Clinical Centre, Auckland District Health Board, Auckland, New Zealand.
¹³ Garvan-Weizmann Centre for Cellular Genomics, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
¹⁴ St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia.
¹⁵ University of Queensland School of Medicine, Brisbane, Queensland, Australia.
¹⁶ Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
¹⁷ Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
¹⁸ Centre for Ophthalmology and Visual Science, University of Western Australia, Crawley, Western Australia, Australia.

PMID: 30054594
DOI: 10.1038/s41588-018-0176-y

Abstract

Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide¹. Both IOP and POAG are highly heritable². We report a combined analysis of participants from the UK Biobank (n = 103,914) and previously published data from the International Glaucoma Genetic Consortium (n = 29,578)^3,4 that identified 101 statistically independent genome-wide-significant SNPs for IOP, 85 of which have not been previously reported^4-12. We examined these SNPs in 11,018 glaucoma cases and 126,069 controls, and 53 SNPs showed evidence of association. Gene-based tests implicated an additional 22 independent genes associated with IOP. We derived an allele score based on the IOP loci and loci influencing optic nerve head morphology. In 1,734 people with advanced glaucoma and 2,938 controls, participants in the top decile of the allele score were at increased risk (odds ratio (OR) = 5.6; 95% confidence interval (CI): 4.1-7.6) of glaucoma relative to the bottom decile.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Genome-Wide Association Study / methods
Genotype
Glaucoma / genetics*
Humans
Intraocular Pressure / genetics*
Male
Polymorphism, Single Nucleotide / genetics
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding