Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

PG Hysi; CY (Ching-Yu) Cheng; Henriët Springelkamp; S Macgregor; JNC Bailey; R Wojciechowski; V Vitart; A Nag; AW Hewitt; R Hohn; C Venturini; A Mirshahi; Wishal Ramdas; G Thorleifsson; E Vithana; CC Khor; AB Stefansson; JM Liao; JL Haines; Najaf Amin; YX Wang; PS Wild; AB Ozel; JZ Li; BW Fleck; T Zeller; SE Staffieri; YY Teo; G Cuellar-Partida; XY Luo; RR Allingham; JE Richards; A Senft; Lennart Karssen; YF Zheng; C Bellenguez; L Xu; AI Iglesias; JF Wilson; JH Kang; Elisa Leeuwen; V Jonsson; U Thorsteinsdottir; Dominiek Despriet; S Ennis; SE Moroi; NG Martin; NM (Nomdo) Jansonius; S Yazar; ES Tai; P Amouyel; J Kirwan; Leonieke Koolwijk; MA Hauser; F Jonasson; P Leo; SJ Loomis; R Fogarty; Fernando Rivadeneira; L Kearns; KJ Lackner; CL Simpson; CE Pennell; Ben Oostra; André Uitterlinden; SM Saw; AJ Lotery; JE Bailey-Wilson; Bert Hofman; Hans Vingerling; C Maubaret; N Pfeiffer; R.C.W. Wolfs; HG Lemij; TL Young; LR Pasquale; C Delcourt; TD Spector; Caroline Klaver; KS Small; KP Burdon; K Stefansson; TY (Tien Yin) Wong; A Viswanathan; DA Mackey; JE Craig; JL Wiggs; Cornelia Duijn; CJ Hammond; T Aung

doi:10.1038/ng.3087

Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

PG Hysi
, CY (Ching-Yu) Cheng
, Henriët Springelkamp
, S Macgregor
, JNC Bailey
, R Wojciechowski
, V Vitart
, A Nag
, AW Hewitt
, R Hohn
, C Venturini
, A Mirshahi
, Wishal Ramdas
, G Thorleifsson
, E Vithana
, CC Khor
, AB Stefansson
, JM Liao
, JL Haines
, Najaf Amin

YX Wang, PS Wild, AB Ozel, JZ Li, BW Fleck, T Zeller, SE Staffieri, YY Teo, G Cuellar-Partida, XY Luo, RR Allingham, JE Richards, A Senft, Lennart Karssen, YF Zheng, C Bellenguez, L Xu, AI Iglesias, JF Wilson, JH Kang, Elisa Leeuwen, V Jonsson, U Thorsteinsdottir, Dominiek Despriet, S Ennis, SE Moroi, NG Martin, NM (Nomdo) Jansonius, S Yazar, ES Tai, P Amouyel, J Kirwan, Leonieke Koolwijk, MA Hauser, F Jonasson, P Leo, SJ Loomis, R Fogarty, Fernando Rivadeneira, L Kearns, KJ Lackner, CL Simpson, CE Pennell, Ben Oostra, André Uitterlinden, SM Saw, AJ Lotery, JE Bailey-Wilson, Bert Hofman, Hans Vingerling, C Maubaret, N Pfeiffer, R.C.W. Wolfs, HG Lemij, TL Young, LR Pasquale, C Delcourt, TD Spector, Caroline Klaver, KS Small, KP Burdon, K Stefansson, TY (Tien Yin) Wong, A Viswanathan, DA Mackey, JE Craig, JL Wiggs, Cornelia Duijn, CJ Hammond, T Aung

External organisation

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

218 Citations (Scopus)

Abstract

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 x 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 x 10(-11) for rs2472493 near ABCA1 and P = 6.39 x 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 x 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.

Original language	Undefined/Unknown
Pages (from-to)	1126-1130
Number of pages	5
Journal	Nature Genetics
Volume	46
Issue number	10
DOIs	https://doi.org/10.1038/ng.3087
Publication status	Published - 2014

Research programs

EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC OR-01-60-01

Access to Document

10.1038/ng.3087

Cite this

Hysi, PG., Cheng, CY., Springelkamp, H., Macgregor, S., Bailey, JNC., Wojciechowski, R., Vitart, V., Nag, A., Hewitt, AW., Hohn, R., Venturini, C., Mirshahi, A., Ramdas, W., Thorleifsson, G., Vithana, E., Khor, CC., Stefansson, AB., Liao, JM., Haines, JL., ... Aung, T. (2014). Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. Nature Genetics, 46(10), 1126-1130. https://doi.org/10.1038/ng.3087

@article{4b8594103363456492949cc3251696e5,

title = "Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma",

abstract = "Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 x 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 x 10(-11) for rs2472493 near ABCA1 and P = 6.39 x 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 x 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.",

author = "PG Hysi and Cheng, \{CY (Ching-Yu)\} and Henri{\"e}t Springelkamp and S Macgregor and JNC Bailey and R Wojciechowski and V Vitart and A Nag and AW Hewitt and R Hohn and C Venturini and A Mirshahi and Wishal Ramdas and G Thorleifsson and E Vithana and CC Khor and AB Stefansson and JM Liao and JL Haines and Najaf Amin and YX Wang and PS Wild and AB Ozel and JZ Li and BW Fleck and T Zeller and SE Staffieri and YY Teo and G Cuellar-Partida and XY Luo and RR Allingham and JE Richards and A Senft and Lennart Karssen and YF Zheng and C Bellenguez and L Xu and AI Iglesias and JF Wilson and JH Kang and Elisa Leeuwen and V Jonsson and U Thorsteinsdottir and Dominiek Despriet and S Ennis and SE Moroi and NG Martin and Jansonius, \{NM (Nomdo)\} and S Yazar and ES Tai and P Amouyel and J Kirwan and Leonieke Koolwijk and MA Hauser and F Jonasson and P Leo and SJ Loomis and R Fogarty and Fernando Rivadeneira and L Kearns and KJ Lackner and CL Simpson and CE Pennell and Ben Oostra and Andr{\'e} Uitterlinden and SM Saw and AJ Lotery and JE Bailey-Wilson and Bert Hofman and Hans Vingerling and C Maubaret and N Pfeiffer and R.C.W. Wolfs and HG Lemij and TL Young and LR Pasquale and C Delcourt and TD Spector and Caroline Klaver and KS Small and KP Burdon and K Stefansson and Wong, \{TY (Tien Yin)\} and A Viswanathan and DA Mackey and JE Craig and JL Wiggs and Cornelia Duijn and CJ Hammond and T Aung",

year = "2014",

doi = "10.1038/ng.3087",

language = "Undefined/Unknown",

volume = "46",

pages = "1126--1130",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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Hysi, PG, Cheng, CY, Springelkamp, H, Macgregor, S, Bailey, JNC, Wojciechowski, R, Vitart, V, Nag, A, Hewitt, AW, Hohn, R, Venturini, C, Mirshahi, A, Ramdas, W, Thorleifsson, G, Vithana, E, Khor, CC, Stefansson, AB, Liao, JM, Haines, JL, Amin, N, Wang, YX, Wild, PS, Ozel, AB, Li, JZ, Fleck, BW, Zeller, T, Staffieri, SE, Teo, YY, Cuellar-Partida, G, Luo, XY, Allingham, RR, Richards, JE, Senft, A, Karssen, L, Zheng, YF, Bellenguez, C, Xu, L, Iglesias, AI, Wilson, JF, Kang, JH, Leeuwen, E, Jonsson, V, Thorsteinsdottir, U, Despriet, D, Ennis, S, Moroi, SE, Martin, NG, Jansonius, NM, Yazar, S, Tai, ES, Amouyel, P, Kirwan, J, Koolwijk, L, Hauser, MA, Jonasson, F, Leo, P, Loomis, SJ, Fogarty, R, Rivadeneira, F, Kearns, L, Lackner, KJ, Simpson, CL, Pennell, CE, Oostra, B, Uitterlinden, A, Saw, SM, Lotery, AJ, Bailey-Wilson, JE, Hofman, B , Vingerling, H, Maubaret, C, Pfeiffer, N, Wolfs, RCW, Lemij, HG, Young, TL, Pasquale, LR, Delcourt, C, Spector, TD, Klaver, C, Small, KS, Burdon, KP, Stefansson, K, Wong, TY, Viswanathan, A, Mackey, DA, Craig, JE, Wiggs, JL, Duijn, C, Hammond, CJ & Aung, T 2014, 'Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma', Nature Genetics, vol. 46, no. 10, pp. 1126-1130. https://doi.org/10.1038/ng.3087

TY - JOUR

T1 - Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

AU - Hysi, PG

AU - Cheng, CY (Ching-Yu)

AU - Springelkamp, Henriët

AU - Macgregor, S

AU - Bailey, JNC

AU - Wojciechowski, R

AU - Vitart, V

AU - Nag, A

AU - Hewitt, AW

AU - Hohn, R

AU - Venturini, C

AU - Mirshahi, A

AU - Ramdas, Wishal

AU - Thorleifsson, G

AU - Vithana, E

AU - Khor, CC

AU - Stefansson, AB

AU - Liao, JM

AU - Haines, JL

AU - Amin, Najaf

AU - Wang, YX

AU - Wild, PS

AU - Ozel, AB

AU - Li, JZ

AU - Fleck, BW

AU - Zeller, T

AU - Staffieri, SE

AU - Teo, YY

AU - Cuellar-Partida, G

AU - Luo, XY

AU - Allingham, RR

AU - Richards, JE

AU - Senft, A

AU - Karssen, Lennart

AU - Zheng, YF

AU - Bellenguez, C

AU - Xu, L

AU - Iglesias, AI

AU - Wilson, JF

AU - Kang, JH

AU - Leeuwen, Elisa

AU - Jonsson, V

AU - Thorsteinsdottir, U

AU - Despriet, Dominiek

AU - Ennis, S

AU - Moroi, SE

AU - Martin, NG

AU - Jansonius, NM (Nomdo)

AU - Yazar, S

AU - Tai, ES

AU - Amouyel, P

AU - Kirwan, J

AU - Koolwijk, Leonieke

AU - Hauser, MA

AU - Jonasson, F

AU - Leo, P

AU - Loomis, SJ

AU - Fogarty, R

AU - Rivadeneira, Fernando

AU - Kearns, L

AU - Lackner, KJ

AU - Simpson, CL

AU - Pennell, CE

AU - Oostra, Ben

AU - Uitterlinden, André

AU - Saw, SM

AU - Lotery, AJ

AU - Bailey-Wilson, JE

AU - Hofman, Bert

AU - Vingerling, Hans

AU - Maubaret, C

AU - Pfeiffer, N

AU - Wolfs, R.C.W.

AU - Lemij, HG

AU - Young, TL

AU - Pasquale, LR

AU - Delcourt, C

AU - Spector, TD

AU - Klaver, Caroline

AU - Small, KS

AU - Burdon, KP

AU - Stefansson, K

AU - Wong, TY (Tien Yin)

AU - Viswanathan, A

AU - Mackey, DA

AU - Craig, JE

AU - Wiggs, JL

AU - Duijn, Cornelia

AU - Hammond, CJ

AU - Aung, T

PY - 2014

Y1 - 2014

N2 - Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 x 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 x 10(-11) for rs2472493 near ABCA1 and P = 6.39 x 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 x 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.

AB - Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 x 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 x 10(-11) for rs2472493 near ABCA1 and P = 6.39 x 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 x 10(-11) for rs747782). Separate meta-analyses of 4 independent POAG cohorts, totaling 4,284 cases and 95,560 controls, showed that 3 of these loci for IOP were also associated with POAG.

U2 - 10.1038/ng.3087

DO - 10.1038/ng.3087

M3 - Article

C2 - 25173106

SN - 1061-4036

VL - 46

SP - 1126

EP - 1130

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -