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

Author(s): MacGregor S (1), Ong JS (2), An J (2), Han X (2), Zhou T (3), Siggs OM (3), Law MH (2), Souzeau E (3), Sharma S (3), Lynn DJ (4,5,6), Beesley J (2), Sheldrick B (3), Mills RA (3), Landers J (3), Ruddle JB (7), Graham SL (8), Healey PR (9,10), White AJR (9), Casson RJ (11), Best S (12), Grigg JR (10), Goldberg I (10), Powell JE (13,14), Whiteman DC (2), Radford-Smith GL (2,15), Martin NG (2), Montgomery GW (16), Burdon KP (3,17), Mackey DA (17,18), Gharahkhani P (2), Craig JE (3), Hewitt AW (7,17)

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.

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 reported4-12. 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.

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

http://www.ncbi.nlm.nih.gov/pubmed/30054594

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