Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

Henriet Springelkamp; Aniket Mishra; Pirro G. Hysi; Puya Gharahkhani; Rene Hoehn; Chiea-Chuen Khor; Jessica N. Cooke Bailey; Xiaoyan Luo; Wishal D. Ramdas; Eranga Vithana; Victor Koh; Seyhan Yazar; Liang Xu; Hannah Forward; Lisa S. Kearns; Najaf Amin; Adriana I. Iglesias; Kar-Seng Sim; Elisabeth M. van Leeuwen; Ayse Demirkan; Sven van der Lee; Seng-Chee Loon; Fernando Rivadeneira; Abhishek Nag; Paul G. Sanfilippo; Arne Schillert; Paulus T. V. M. de Jong; Ben A. Oostra; Andre G. Uitterlinden; Albert Hofman; Tiger Zhou; Kathryn P. Burdon; Timothy D. Spector; Karl J. Lackner; Seang-Mei Saw; Johannes R. Vingerling; Yik-Ying Teo; Louis R. Pasquale; Roger C. W. Wolfs; Hans G. Lemij; E-Shyong Tai; Jost B. Jonas; Ching-Yu Cheng; Tin Aung; Nomdo M. Jansonius; Caroline C. W. Klaver; Jamie E. Craig; Terri L. Young; Jonathan L. Haines; Stuart MacGregor; David A. Mackey; Norbert Pfeiffer; Tien-Yin Wong; Janey L. Wiggs; Alex W. Hewitt; Cornelia M. van Duijn; Christopher J. Hammond

doi:10.1002/gepi.21886

Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

Henriet Springelkamp^*, Aniket Mishra, Pirro G. Hysi, Puya Gharahkhani, Rene Hoehn, Chiea-Chuen Khor, Jessica N. Cooke Bailey, Xiaoyan Luo, Wishal D. Ramdas, Eranga Vithana, Victor Koh, Seyhan Yazar, Liang Xu, Hannah Forward, Lisa S. Kearns, Najaf Amin, Adriana I. Iglesias, Kar-Seng Sim, Elisabeth M. van Leeuwen, Ayse DemirkanSven van der Lee, Seng-Chee Loon, Fernando Rivadeneira, Abhishek Nag, Paul G. Sanfilippo, Arne Schillert, Paulus T. V. M. de Jong, Ben A. Oostra, Andre G. Uitterlinden, Albert Hofman, Tiger Zhou, Kathryn P. Burdon, Timothy D. Spector, Karl J. Lackner, Seang-Mei Saw, Johannes R. Vingerling, Yik-Ying Teo, Louis R. Pasquale, Roger C. W. Wolfs, Hans G. Lemij, E-Shyong Tai, Jost B. Jonas, Ching-Yu Cheng, Tin Aung, Nomdo M. Jansonius, Caroline C. W. Klaver, Jamie E. Craig, Terri L. Young, Jonathan L. Haines, Stuart MacGregor, David A. Mackey, Norbert Pfeiffer, Tien-Yin Wong, Janey L. Wiggs, Alex W. Hewitt, Cornelia M. van Duijn, Christopher J. Hammond

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

55 Citations (Web of Science)

Abstract

Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma. ? 2015

Original language	English
Pages (from-to)	207-216
Journal	Genetic Epidemiology
Volume	39
Issue number	3
DOIs	https://doi.org/10.1002/gepi.21886
Publication status	Published - Mar 2015

Keywords

GWAS
disc area
cup area
glaucoma

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10.1002/gepi.21886

Cite this

Springelkamp, H., Mishra, A., Hysi, P. G., Gharahkhani, P., Hoehn, R., Khor, C-C., Bailey, J. N. C., Luo, X., Ramdas, W. D., Vithana, E., Koh, V., Yazar, S., Xu, L., Forward, H., Kearns, L. S., Amin, N., Iglesias, A. I., Sim, K-S., van Leeuwen, E. M., ... Hammond, C. J. (2015). Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology. Genetic Epidemiology, 39(3), 207-216. https://doi.org/10.1002/gepi.21886

@article{11167504c5bf404e92ff1ae4d5127a0e,

title = "Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology",

abstract = "Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma. ? 2015",

keywords = "GWAS, disc area, cup area, glaucoma",

author = "Henriet Springelkamp and Aniket Mishra and Hysi, {Pirro G.} and Puya Gharahkhani and Rene Hoehn and Chiea-Chuen Khor and Bailey, {Jessica N. Cooke} and Xiaoyan Luo and Ramdas, {Wishal D.} and Eranga Vithana and Victor Koh and Seyhan Yazar and Liang Xu and Hannah Forward and Kearns, {Lisa S.} and Najaf Amin and Iglesias, {Adriana I.} and Kar-Seng Sim and {van Leeuwen}, {Elisabeth M.} and Ayse Demirkan and {van der Lee}, Sven and Seng-Chee Loon and Fernando Rivadeneira and Abhishek Nag and Sanfilippo, {Paul G.} and Arne Schillert and {de Jong}, {Paulus T. V. M.} and Oostra, {Ben A.} and Uitterlinden, {Andre G.} and Albert Hofman and Tiger Zhou and Burdon, {Kathryn P.} and Spector, {Timothy D.} and Lackner, {Karl J.} and Seang-Mei Saw and Vingerling, {Johannes R.} and Yik-Ying Teo and Pasquale, {Louis R.} and Wolfs, {Roger C. W.} and Lemij, {Hans G.} and E-Shyong Tai and Jonas, {Jost B.} and Ching-Yu Cheng and Tin Aung and Jansonius, {Nomdo M.} and Klaver, {Caroline C. W.} and Craig, {Jamie E.} and Young, {Terri L.} and Haines, {Jonathan L.} and Stuart MacGregor and Mackey, {David A.} and Norbert Pfeiffer and Tien-Yin Wong and Wiggs, {Janey L.} and Hewitt, {Alex W.} and {van Duijn}, {Cornelia M.} and Hammond, {Christopher J.}",

year = "2015",

month = mar,

doi = "10.1002/gepi.21886",

language = "English",

volume = "39",

pages = "207--216",

journal = "Genetic Epidemiology",

issn = "0741-0395",

publisher = "Wiley-Blackwell",

number = "3",

}

Springelkamp, H, Mishra, A, Hysi, PG, Gharahkhani, P, Hoehn, R, Khor, C-C, Bailey, JNC, Luo, X, Ramdas, WD, Vithana, E, Koh, V, Yazar, S, Xu, L, Forward, H, Kearns, LS, Amin, N, Iglesias, AI, Sim, K-S, van Leeuwen, EM, Demirkan, A, van der Lee, S, Loon, S-C, Rivadeneira, F, Nag, A, Sanfilippo, PG, Schillert, A, de Jong, PTVM, Oostra, BA, Uitterlinden, AG, Hofman, A, Zhou, T, Burdon, KP, Spector, TD, Lackner, KJ, Saw, S-M, Vingerling, JR, Teo, Y-Y, Pasquale, LR, Wolfs, RCW, Lemij, HG, Tai, E-S, Jonas, JB, Cheng, C-Y, Aung, T, Jansonius, NM, Klaver, CCW, Craig, JE, Young, TL, Haines, JL, MacGregor, S, Mackey, DA, Pfeiffer, N, Wong, T-Y, Wiggs, JL, Hewitt, AW, van Duijn, CM & Hammond, CJ 2015, 'Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology', Genetic Epidemiology, vol. 39, no. 3, pp. 207-216. https://doi.org/10.1002/gepi.21886

TY - JOUR

T1 - Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic Disc Morphology

AU - Springelkamp, Henriet

AU - Mishra, Aniket

AU - Hysi, Pirro G.

AU - Gharahkhani, Puya

AU - Hoehn, Rene

AU - Khor, Chiea-Chuen

AU - Bailey, Jessica N. Cooke

AU - Luo, Xiaoyan

AU - Ramdas, Wishal D.

AU - Vithana, Eranga

AU - Koh, Victor

AU - Yazar, Seyhan

AU - Xu, Liang

AU - Forward, Hannah

AU - Kearns, Lisa S.

AU - Amin, Najaf

AU - Iglesias, Adriana I.

AU - Sim, Kar-Seng

AU - van Leeuwen, Elisabeth M.

AU - Demirkan, Ayse

AU - van der Lee, Sven

AU - Loon, Seng-Chee

AU - Rivadeneira, Fernando

AU - Nag, Abhishek

AU - Sanfilippo, Paul G.

AU - Schillert, Arne

AU - de Jong, Paulus T. V. M.

AU - Oostra, Ben A.

AU - Uitterlinden, Andre G.

AU - Hofman, Albert

AU - Zhou, Tiger

AU - Burdon, Kathryn P.

AU - Spector, Timothy D.

AU - Lackner, Karl J.

AU - Saw, Seang-Mei

AU - Vingerling, Johannes R.

AU - Teo, Yik-Ying

AU - Pasquale, Louis R.

AU - Wolfs, Roger C. W.

AU - Lemij, Hans G.

AU - Tai, E-Shyong

AU - Jonas, Jost B.

AU - Cheng, Ching-Yu

AU - Aung, Tin

AU - Jansonius, Nomdo M.

AU - Klaver, Caroline C. W.

AU - Craig, Jamie E.

AU - Young, Terri L.

AU - Haines, Jonathan L.

AU - MacGregor, Stuart

AU - Mackey, David A.

AU - Pfeiffer, Norbert

AU - Wong, Tien-Yin

AU - Wiggs, Janey L.

AU - Hewitt, Alex W.

AU - van Duijn, Cornelia M.

AU - Hammond, Christopher J.

PY - 2015/3

Y1 - 2015/3

N2 - Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma. ? 2015

AB - Primary open-angle glaucoma is the most common optic neuropathy and an important cause of irreversible blindness worldwide. The optic nerve head or optic disc is divided in two parts: a central cup (without nerve fibers) surrounded by the neuroretinal rim (containing axons of the retinal ganglion cells). The International Glaucoma Genetics Consortium conducted a meta-analysis of genome-wide association studies consisting of 17,248 individuals of European ancestry and 6,841 individuals of Asian ancestry. The outcomes of the genome-wide association studies were disc area and cup area. These specific measurements describe optic nerve morphology in another way than the vertical cup-disc ratio, which is a clinically used measurement, and may shed light on new glaucoma mechanisms. We identified 10 new loci associated with disc area (CDC42BPA, F5, DIRC3, RARB, ABI3BP, DCAF4L2, ELP4, TMTC2, NR2F2, and HORMAD2) and another 10 new loci associated with cup area (DHRS3, TRIB2, EFEMP1, FLNB, FAM101, DDHD1, ASB7, KPNB1, BCAS3, and TRIOBP). The new genes participate in a number of pathways and future work is likely to identify more functions related to the pathogenesis of glaucoma. ? 2015

KW - GWAS

KW - disc area

KW - cup area

KW - glaucoma

U2 - 10.1002/gepi.21886

DO - 10.1002/gepi.21886

M3 - Article

C2 - 25631615

SN - 0741-0395

VL - 39

SP - 207

EP - 216

JO - Genetic Epidemiology

JF - Genetic Epidemiology

IS - 3

ER -