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

Stuart MacGregor; Jue Sheng Ong; Jiyuan An; Xikun Han; Tiger Zhou; Owen Marc Siggs; Matthew H. Law; Emmanuelle Souzeau; Shiwani C. Sharma; David J. Lynn; Jonathan Beesley; Bronwyn Sheldrick; Richard A.D. Mills; John A. Landers; Jonathan B. Ruddle; Stuart L. Graham; Paul R. Healey; Andrew J.R. White; Robert J. Casson; Stephen J. 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 Evan Craig; A. W. Hewitt

doi:10.1038/s41588-018-0176-y

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

Stuart MacGregor, Jue Sheng Ong, Jiyuan An, Xikun Han, Tiger Zhou, Owen Marc Siggs, Matthew H. Law, Emmanuelle Souzeau, Shiwani C. Sharma, David J. Lynn, Jonathan Beesley, Bronwyn Sheldrick, Richard A.D. Mills, John A. Landers, Jonathan B. Ruddle, Stuart L. Graham, Paul R. Healey, Andrew J.R. White, Robert J. Casson, Stephen J. BestJohn 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 Evan Craig, A. W. Hewitt

College of Medicine and Public Health

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

101 Citations (Scopus)

Abstract

Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide ¹ . Both IOP and POAG are highly heritable ² . 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.

Original language	English
Pages (from-to)	1067-1071
Number of pages	5
Journal	Nature Genetics
Volume	50
Issue number	8
DOIs	https://doi.org/10.1038/s41588-018-0176-y
Publication status	Published - 1 Aug 2018

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MacGregor, S., Ong, J. S., An, J., Han, X., Zhou, T., Siggs, O. M., Law, M. H., Souzeau, E., Sharma, S. C., Lynn, D. J., Beesley, J., Sheldrick, B., Mills, R. A. D., Landers, J. A., Ruddle, J. B., Graham, S. L., Healey, P. R., White, A. J. R., Casson, R. J., ... Hewitt, A. W. (2018). Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma. Nature Genetics, 50(8), 1067-1071. https://doi.org/10.1038/s41588-018-0176-y

@article{6f94c4d7f569479e82e3b20a946ed91e,

title = "Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma",

abstract = " Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide 1 . Both IOP and POAG are highly heritable 2 . 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. ",

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

year = "2018",

month = aug,

day = "1",

doi = "10.1038/s41588-018-0176-y",

language = "English",

volume = "50",

pages = "1067--1071",

journal = "Nature Genetics",

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MacGregor, S, Ong, JS, An, J, Han, X, Zhou, T, Siggs, OM, Law, MH, Souzeau, E, Sharma, SC, Lynn, DJ, Beesley, J, Sheldrick, B, Mills, RAD , Landers, JA, Ruddle, JB, Graham, SL, Healey, PR, White, AJR, Casson, RJ, Best, SJ, Grigg, JR, Goldberg, I, Powell, JE, Whiteman, DC, Radford –Smith, GL, Martin, NG, Montgomery, GW, Burdon, KP, Mackey, DA, Gharahkhani, P, Craig, JE & Hewitt, AW 2018, 'Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma', Nature Genetics, vol. 50, no. 8, pp. 1067-1071. https://doi.org/10.1038/s41588-018-0176-y

TY - JOUR

T1 - Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma

AU - MacGregor, Stuart

AU - Ong, Jue Sheng

AU - An, Jiyuan

AU - Han, Xikun

AU - Zhou, Tiger

AU - Siggs, Owen Marc

AU - Law, Matthew H.

AU - Souzeau, Emmanuelle

AU - Sharma, Shiwani C.

AU - Lynn, David J.

AU - Beesley, Jonathan

AU - Sheldrick, Bronwyn

AU - Mills, Richard A.D.

AU - Landers, John A.

AU - Ruddle, Jonathan B.

AU - Graham, Stuart L.

AU - Healey, Paul R.

AU - White, Andrew J.R.

AU - Casson, Robert J.

AU - Best, Stephen J.

AU - Grigg, John R.

AU - Goldberg, Ivan

AU - Powell, Joseph E.

AU - Whiteman, David C.

AU - Radford –Smith, Graham L.

AU - Martin, Nicholas G.

AU - Montgomery, Grant W.

AU - Burdon, Kathryn P.

AU - Mackey, David A.

AU - Gharahkhani, Puya

AU - Craig, Jamie Evan

AU - Hewitt, A. W.

PY - 2018/8/1

Y1 - 2018/8/1

N2 - Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide 1 . Both IOP and POAG are highly heritable 2 . 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.

AB - Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide 1 . Both IOP and POAG are highly heritable 2 . 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.

UR - http://purl.org/au-research/grants/NHMRC/110709

UR - http://purl.org/au-research/grants/NHMRC/1116360

UR - http://purl.org/au-research/grants/NHMRC/1116495

UR - http://purl.org/au-research/grants/NHMRC/1023911

UR - http://www.scopus.com/inward/record.url?scp=85050905900&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0176-y

DO - 10.1038/s41588-018-0176-y

M3 - Letter

SN - 1061-4036

VL - 50

SP - 1067

EP - 1071

JO - Nature Genetics

JF - Nature Genetics

IS - 8

ER -

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

Abstract

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