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

Pirro G Hysi; Ching-Yu Cheng; Henriët Springelkamp; Stuart Macgregor; Jessica N Cooke Bailey; Robert Wojciechowski; Veronique Vitart; Abhishek Nag; Alex W Hewitt; René Höhn; Cristina Venturini; Alireza Mirshahi; Wishal D Ramdas; Gudmar Thorleifsson; Eranga Vithana; Chiea-Chuen Khor; Arni B Stefansson; Jiemin Liao; Jonathan L Haines; Najaf Amin; Ya Xing Wang; Philipp S Wild; Ayse B Ozel; Jun Z Li; Brian W Fleck; Tanja Zeller; Sandra E Staffieri; Yik-Ying Teo; Gabriel Cuellar-Partida; Xiaoyan Luo; R Rand Allingham; Julia E Richards; Andrea Senft; Lennart C Karssen; Yingfeng Zheng; Céline Bellenguez; Liang Xu; Adriana I Iglesias; James F Wilson; Jae H Kang; Elisabeth M van Leeuwen; Vesteinn Jonsson; Unnur Thorsteinsdottir; Dominiek D G Despriet; Sarah Ennis; Sayoko E Moroi; Nicholas G Martin; Nomdo M Jansonius; Leonieke M E van Koolwijk; Hans G Lemij

doi:10.1038/ng.3087

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

Pirro G Hysi, Ching-Yu Cheng, Henriët Springelkamp, Stuart Macgregor, Jessica N Cooke Bailey, Robert Wojciechowski, Veronique Vitart, Abhishek Nag, Alex W Hewitt, René Höhn, Cristina Venturini, Alireza Mirshahi, Wishal D Ramdas, Gudmar Thorleifsson, Eranga Vithana, Chiea-Chuen Khor, Arni B Stefansson, Jiemin Liao, Jonathan L Haines, Najaf AminYa Xing Wang, Philipp S Wild, Ayse B Ozel, Jun Z Li, Brian W Fleck, Tanja Zeller, Sandra E Staffieri, Yik-Ying Teo, Gabriel Cuellar-Partida, Xiaoyan Luo, R Rand Allingham, Julia E Richards, Andrea Senft, Lennart C Karssen, Yingfeng Zheng, Céline Bellenguez, Liang Xu, Adriana I Iglesias, James F Wilson, Jae H Kang, Elisabeth M van Leeuwen, Vesteinn Jonsson, Unnur Thorsteinsdottir, Dominiek D G Despriet, Sarah Ennis, Sayoko E Moroi, Nicholas G Martin, Nomdo M Jansonius, Leonieke M E van Koolwijk, Hans G Lemij,

Glaucoma

Research output: Contribution to journal › Review article › peer-review

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 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 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	English
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 - Oct 2014

Keywords

ABO Blood-Group System/genetics
ATP Binding Cassette Transporter 1/genetics
Adult
Aged
Aged, 80 and over
Chromosomes, Human, Pair 11/genetics
Chromosomes, Human, Pair 3/genetics
Chromosomes, Human, Pair 9/genetics
Cohort Studies
Female
Fibronectins/genetics
Genetic Loci/genetics
Genetic Predisposition to Disease/genetics
Genome-Wide Association Study
Genotype
Glaucoma/genetics
Glaucoma, Open-Angle/genetics
Humans
Intraocular Pressure/genetics
Male
Meta-Analysis as Topic
Middle Aged
Polymorphism, Single Nucleotide
Risk Factors
Young Adult

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10.1038/ng.3087

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Hysi, P. G., Cheng, C.-Y., Springelkamp, H., Macgregor, S., Bailey, J. N. C., Wojciechowski, R., Vitart, V., Nag, A., Hewitt, A. W., Höhn, R., Venturini, C., Mirshahi, A., Ramdas, W. D., Thorleifsson, G., Vithana, E., Khor, C.-C., Stefansson, A. B., Liao, J., Haines, J. L. (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{4757258b050049ceb678466ae0a92b45,

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 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 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.",

keywords = "ABO Blood-Group System/genetics, ATP Binding Cassette Transporter 1/genetics, Adult, Aged, Aged, 80 and over, Chromosomes, Human, Pair 11/genetics, Chromosomes, Human, Pair 3/genetics, Chromosomes, Human, Pair 9/genetics, Cohort Studies, Female, Fibronectins/genetics, Genetic Loci/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study, Genotype, Glaucoma/genetics, Glaucoma, Open-Angle/genetics, Humans, Intraocular Pressure/genetics, Male, Meta-Analysis as Topic, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Young Adult",

author = "Hysi, {Pirro G} and Ching-Yu Cheng and Henri{\"e}t Springelkamp and Stuart Macgregor and Bailey, {Jessica N Cooke} and Robert Wojciechowski and Veronique Vitart and Abhishek Nag and Hewitt, {Alex W} and Ren{\'e} H{\"o}hn and Cristina Venturini and Alireza Mirshahi and Ramdas, {Wishal D} and Gudmar Thorleifsson and Eranga Vithana and Chiea-Chuen Khor and Stefansson, {Arni B} and Jiemin Liao and Haines, {Jonathan L} and Najaf Amin and Wang, {Ya Xing} and Wild, {Philipp S} and Ozel, {Ayse B} and Li, {Jun Z} and Fleck, {Brian W} and Tanja Zeller and Staffieri, {Sandra E} and Yik-Ying Teo and Gabriel Cuellar-Partida and Xiaoyan Luo and Allingham, {R Rand} and Richards, {Julia E} and Andrea Senft and Karssen, {Lennart C} and Yingfeng Zheng and C{\'e}line Bellenguez and Liang Xu and Iglesias, {Adriana I} and Wilson, {James F} and Kang, {Jae H} and {van Leeuwen}, {Elisabeth M} and Vesteinn Jonsson and Unnur Thorsteinsdottir and Despriet, {Dominiek D G} and Sarah Ennis and Moroi, {Sayoko E} and Martin, {Nicholas G} and Jansonius, {Nomdo M} and {van Koolwijk}, {Leonieke M E} and Lemij, {Hans G}",

year = "2014",

month = oct,

doi = "10.1038/ng.3087",

language = "English",

volume = "46",

pages = "1126--1130",

number = "10",

}

Hysi, PG, Cheng, C-Y, Springelkamp, H, Macgregor, S, Bailey, JNC, Wojciechowski, R, Vitart, V, Nag, A, Hewitt, AW, Höhn, R, Venturini, C, Mirshahi, A, Ramdas, WD, Thorleifsson, G, Vithana, E, Khor, C-C, Stefansson, AB, Liao, J, Haines, JL, Amin, N, Wang, YX, Wild, PS, Ozel, AB, Li, JZ, Fleck, BW, Zeller, T, Staffieri, SE, Teo, Y-Y, Cuellar-Partida, G, Luo, X, Allingham, RR, Richards, JE, Senft, A, Karssen, LC, Zheng, Y, Bellenguez, C, Xu, L, Iglesias, AI, Wilson, JF, Kang, JH, van Leeuwen, EM, Jonsson, V, Thorsteinsdottir, U, Despriet, DDG, Ennis, S, Moroi, SE, Martin, NG, Jansonius, NM, van Koolwijk, LME, Lemij, HG 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, Pirro G

AU - Cheng, Ching-Yu

AU - Springelkamp, Henriët

AU - Macgregor, Stuart

AU - Bailey, Jessica N Cooke

AU - Wojciechowski, Robert

AU - Vitart, Veronique

AU - Nag, Abhishek

AU - Hewitt, Alex W

AU - Höhn, René

AU - Venturini, Cristina

AU - Mirshahi, Alireza

AU - Ramdas, Wishal D

AU - Thorleifsson, Gudmar

AU - Vithana, Eranga

AU - Khor, Chiea-Chuen

AU - Stefansson, Arni B

AU - Liao, Jiemin

AU - Haines, Jonathan L

AU - Amin, Najaf

AU - Wang, Ya Xing

AU - Wild, Philipp S

AU - Ozel, Ayse B

AU - Li, Jun Z

AU - Fleck, Brian W

AU - Zeller, Tanja

AU - Staffieri, Sandra E

AU - Teo, Yik-Ying

AU - Cuellar-Partida, Gabriel

AU - Luo, Xiaoyan

AU - Allingham, R Rand

AU - Richards, Julia E

AU - Senft, Andrea

AU - Karssen, Lennart C

AU - Zheng, Yingfeng

AU - Bellenguez, Céline

AU - Xu, Liang

AU - Iglesias, Adriana I

AU - Wilson, James F

AU - Kang, Jae H

AU - van Leeuwen, Elisabeth M

AU - Jonsson, Vesteinn

AU - Thorsteinsdottir, Unnur

AU - Despriet, Dominiek D G

AU - Ennis, Sarah

AU - Moroi, Sayoko E

AU - Martin, Nicholas G

AU - Jansonius, Nomdo M

AU - van Koolwijk, Leonieke M E

AU - Lemij, Hans G

PY - 2014/10

Y1 - 2014/10

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 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 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 × 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 × 10(-11) for rs2472493 near ABCA1 and P = 6.39 × 10(-11) for rs8176693 within ABO) and one on chromosome 11p11.2 (best P = 1.04 × 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.

KW - ABO Blood-Group System/genetics

KW - ATP Binding Cassette Transporter 1/genetics

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Chromosomes, Human, Pair 11/genetics

KW - Chromosomes, Human, Pair 3/genetics

KW - Chromosomes, Human, Pair 9/genetics

KW - Cohort Studies

KW - Female

KW - Fibronectins/genetics

KW - Genetic Loci/genetics

KW - Genetic Predisposition to Disease/genetics

KW - Genome-Wide Association Study

KW - Genotype

KW - Glaucoma/genetics

KW - Glaucoma, Open-Angle/genetics

KW - Humans

KW - Intraocular Pressure/genetics

KW - Male

KW - Meta-Analysis as Topic

KW - Middle Aged

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - Young Adult

UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4177225/pdf/emss-59965.pdf

U2 - 10.1038/ng.3087

DO - 10.1038/ng.3087

M3 - Review article

C2 - 25173106

SN - 1061-4036

VL - 46

SP - 1126

EP - 1130

JO - Nature Genetics

JF - Nature Genetics

IS - 10

ER -

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

Abstract

Keywords

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