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

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MacGregor, Stuart
Ong, Jue Sheng
An, Jiyuan
Han, Xikun
Zhou, Tiger
Siggs, Owen M
Law, Matthew H
Souzeau, Emmanuelle
Sharma, Shiwani
Lynn, David J
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Springer Nature
© 2018 Springer Nature Limited.
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Springer Nature Limited.
Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide. Both IOP and POAG are highly heritable. 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) that identified 101 statistically independent genome-wide-significant SNPs for IOP, 85 of which have not been previously reported. 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.
This article has been archived in accordance with the publisher's policy. © 2018 Springer Nature Limited. This author accepted manuscript is made available following 6 month embargo from date of publication (July 2018) in accordance with the publisher’s copyright policy
Intraocular pressure (IOP), glaucoma, primary open-angle glaucoma (POAG), blindness, International Glaucoma Genetic Consortium, Gene-based tests
MacGregor, S., Ong, J.-S., An, J., Han, X., Zhou, T., Siggs, O. M., … Hewitt, A. W. (2018). Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma. Nature Genetics, 50(8), 1067–1071.