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Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

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Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. / Iglesias, Adriana I; Mishra, Aniket; Vitart, Veronique; Bykhovskaya, Yelena; Höhn, René; Springelkamp, Henriët; Cuellar-Partida, Gabriel; Gharahkhani, Puya; Bailey, Jessica N Cooke; Willoughby, Colin E; Li, Xiaohui; Yazar, Seyhan; Nag, Abhishek; Khawaja, Anthony P; Polašek, Ozren; Siscovick, David; Mitchell, Paul; Tham, Yih Chung; Haines, Jonathan L; Kearns, Lisa S; Hayward, Caroline; Shi, Yuan; van Leeuwen, Elisabeth M; Taylor, Kent D; Bonnemaijer, Pieter; Rotter, Jerome I; Martin, Nicholas G; Zeller, Tanja; Mills, Richard A; Souzeau, Emmanuelle; Staffieri, Sandra E; Jonas, Jost B; Schmidtmann, Irene; Boutin, Thibaud; Kang, Jae H; Lucas, Sionne E M; Wong, Tien Yin; Beutel, Manfred E; Wilson, James F; Uitterlinden, André G; Vithana, Eranga N; Foster, Paul J; Hysi, Pirro G; Hewitt, Alex W; Khor, Chiea Chuen; Pasquale, Louis R; Montgomery, Grant W; Klaver, Caroline C W; Aung, Tin; Pfeiffer, Norbert; Mackey, David A; Hammond, Christopher J; Cheng, Ching-Yu; Craig, Jamie E; Rabinowitz, Yaron S; Wiggs, Janey L; Burdon, Kathryn P; van Duijn, Cornelia M; MacGregor, Stuart; Blue Mountains Eye Study—GWAS group.

in: NAT COMMUN, Jahrgang 9, Nr. 1, 14.05.2018, S. 1864.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Iglesias, AI, Mishra, A, Vitart, V, Bykhovskaya, Y, Höhn, R, Springelkamp, H, Cuellar-Partida, G, Gharahkhani, P, Bailey, JNC, Willoughby, CE, Li, X, Yazar, S, Nag, A, Khawaja, AP, Polašek, O, Siscovick, D, Mitchell, P, Tham, YC, Haines, JL, Kearns, LS, Hayward, C, Shi, Y, van Leeuwen, EM, Taylor, KD, Bonnemaijer, P, Rotter, JI, Martin, NG, Zeller, T, Mills, RA, Souzeau, E, Staffieri, SE, Jonas, JB, Schmidtmann, I, Boutin, T, Kang, JH, Lucas, SEM, Wong, TY, Beutel, ME, Wilson, JF, Uitterlinden, AG, Vithana, EN, Foster, PJ, Hysi, PG, Hewitt, AW, Khor, CC, Pasquale, LR, Montgomery, GW, Klaver, CCW, Aung, T, Pfeiffer, N, Mackey, DA, Hammond, CJ, Cheng, C-Y, Craig, JE, Rabinowitz, YS, Wiggs, JL, Burdon, KP, van Duijn, CM, MacGregor, S & Blue Mountains Eye Study—GWAS group 2018, 'Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases', NAT COMMUN, Jg. 9, Nr. 1, S. 1864. https://doi.org/10.1038/s41467-018-03646-6

APA

Iglesias, A. I., Mishra, A., Vitart, V., Bykhovskaya, Y., Höhn, R., Springelkamp, H., Cuellar-Partida, G., Gharahkhani, P., Bailey, J. N. C., Willoughby, C. E., Li, X., Yazar, S., Nag, A., Khawaja, A. P., Polašek, O., Siscovick, D., Mitchell, P., Tham, Y. C., Haines, J. L., ... Blue Mountains Eye Study—GWAS group (2018). Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. NAT COMMUN, 9(1), 1864. https://doi.org/10.1038/s41467-018-03646-6

Vancouver

Iglesias AI, Mishra A, Vitart V, Bykhovskaya Y, Höhn R, Springelkamp H et al. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. NAT COMMUN. 2018 Mai 14;9(1):1864. https://doi.org/10.1038/s41467-018-03646-6

Bibtex

@article{58b5ede2257241f8add8266e699bcbce,
title = "Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases",
abstract = "Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.",
keywords = "ADAMTS Proteins/genetics, Asian Continental Ancestry Group, Cornea/abnormalities, Corneal Diseases/ethnology, Corneal Dystrophies, Hereditary/ethnology, Decorin/genetics, Ehlers-Danlos Syndrome/ethnology, European Continental Ancestry Group, Eye Diseases, Hereditary/ethnology, Fibrillin-1/genetics, Gene Expression, Genome, Human, Genome-Wide Association Study, Glaucoma, Open-Angle/ethnology, Humans, Keratoconus/ethnology, Loeys-Dietz Syndrome/ethnology, Lumican/genetics, Marfan Syndrome/ethnology, Mendelian Randomization Analysis, Myopia/ethnology, Polymorphism, Single Nucleotide, Proteoglycans/genetics, Quantitative Trait Loci, Quantitative Trait, Heritable, Transforming Growth Factor beta2/genetics",
author = "Iglesias, {Adriana I} and Aniket Mishra and Veronique Vitart and Yelena Bykhovskaya and Ren{\'e} H{\"o}hn and Henri{\"e}t Springelkamp and Gabriel Cuellar-Partida and Puya Gharahkhani and Bailey, {Jessica N Cooke} and Willoughby, {Colin E} and Xiaohui Li and Seyhan Yazar and Abhishek Nag and Khawaja, {Anthony P} and Ozren Pola{\v s}ek and David Siscovick and Paul Mitchell and Tham, {Yih Chung} and Haines, {Jonathan L} and Kearns, {Lisa S} and Caroline Hayward and Yuan Shi and {van Leeuwen}, {Elisabeth M} and Taylor, {Kent D} and Pieter Bonnemaijer and Rotter, {Jerome I} and Martin, {Nicholas G} and Tanja Zeller and Mills, {Richard A} and Emmanuelle Souzeau and Staffieri, {Sandra E} and Jonas, {Jost B} and Irene Schmidtmann and Thibaud Boutin and Kang, {Jae H} and Lucas, {Sionne E M} and Wong, {Tien Yin} and Beutel, {Manfred E} and Wilson, {James F} and Uitterlinden, {Andr{\'e} G} and Vithana, {Eranga N} and Foster, {Paul J} and Hysi, {Pirro G} and Hewitt, {Alex W} and Khor, {Chiea Chuen} and Pasquale, {Louis R} and Montgomery, {Grant W} and Klaver, {Caroline C W} and Tin Aung and Norbert Pfeiffer and Mackey, {David A} and Hammond, {Christopher J} and Ching-Yu Cheng and Craig, {Jamie E} and Rabinowitz, {Yaron S} and Wiggs, {Janey L} and Burdon, {Kathryn P} and {van Duijn}, {Cornelia M} and Stuart MacGregor and {Blue Mountains Eye Study—GWAS group}",
year = "2018",
month = may,
day = "14",
doi = "10.1038/s41467-018-03646-6",
language = "English",
volume = "9",
pages = "1864",
journal = "NAT COMMUN",
issn = "2041-1723",
publisher = "NATURE PUBLISHING GROUP",
number = "1",

}

RIS

TY - JOUR

T1 - Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases

AU - Iglesias, Adriana I

AU - Mishra, Aniket

AU - Vitart, Veronique

AU - Bykhovskaya, Yelena

AU - Höhn, René

AU - Springelkamp, Henriët

AU - Cuellar-Partida, Gabriel

AU - Gharahkhani, Puya

AU - Bailey, Jessica N Cooke

AU - Willoughby, Colin E

AU - Li, Xiaohui

AU - Yazar, Seyhan

AU - Nag, Abhishek

AU - Khawaja, Anthony P

AU - Polašek, Ozren

AU - Siscovick, David

AU - Mitchell, Paul

AU - Tham, Yih Chung

AU - Haines, Jonathan L

AU - Kearns, Lisa S

AU - Hayward, Caroline

AU - Shi, Yuan

AU - van Leeuwen, Elisabeth M

AU - Taylor, Kent D

AU - Bonnemaijer, Pieter

AU - Rotter, Jerome I

AU - Martin, Nicholas G

AU - Zeller, Tanja

AU - Mills, Richard A

AU - Souzeau, Emmanuelle

AU - Staffieri, Sandra E

AU - Jonas, Jost B

AU - Schmidtmann, Irene

AU - Boutin, Thibaud

AU - Kang, Jae H

AU - Lucas, Sionne E M

AU - Wong, Tien Yin

AU - Beutel, Manfred E

AU - Wilson, James F

AU - Uitterlinden, André G

AU - Vithana, Eranga N

AU - Foster, Paul J

AU - Hysi, Pirro G

AU - Hewitt, Alex W

AU - Khor, Chiea Chuen

AU - Pasquale, Louis R

AU - Montgomery, Grant W

AU - Klaver, Caroline C W

AU - Aung, Tin

AU - Pfeiffer, Norbert

AU - Mackey, David A

AU - Hammond, Christopher J

AU - Cheng, Ching-Yu

AU - Craig, Jamie E

AU - Rabinowitz, Yaron S

AU - Wiggs, Janey L

AU - Burdon, Kathryn P

AU - van Duijn, Cornelia M

AU - MacGregor, Stuart

AU - Blue Mountains Eye Study—GWAS group

PY - 2018/5/14

Y1 - 2018/5/14

N2 - Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

AB - Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

KW - ADAMTS Proteins/genetics

KW - Asian Continental Ancestry Group

KW - Cornea/abnormalities

KW - Corneal Diseases/ethnology

KW - Corneal Dystrophies, Hereditary/ethnology

KW - Decorin/genetics

KW - Ehlers-Danlos Syndrome/ethnology

KW - European Continental Ancestry Group

KW - Eye Diseases, Hereditary/ethnology

KW - Fibrillin-1/genetics

KW - Gene Expression

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Glaucoma, Open-Angle/ethnology

KW - Humans

KW - Keratoconus/ethnology

KW - Loeys-Dietz Syndrome/ethnology

KW - Lumican/genetics

KW - Marfan Syndrome/ethnology

KW - Mendelian Randomization Analysis

KW - Myopia/ethnology

KW - Polymorphism, Single Nucleotide

KW - Proteoglycans/genetics

KW - Quantitative Trait Loci

KW - Quantitative Trait, Heritable

KW - Transforming Growth Factor beta2/genetics

U2 - 10.1038/s41467-018-03646-6

DO - 10.1038/s41467-018-03646-6

M3 - SCORING: Journal article

C2 - 29760442

VL - 9

SP - 1864

JO - NAT COMMUN

JF - NAT COMMUN

SN - 2041-1723

IS - 1

ER -