Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos

International Glaucoma Genetics Consortium; Xiaoyi Gao; Drew R. Nannini; Kristen Corrao; Mina Torres; Yii Der I. Chen; Bao J. Fan; Janey L. Wiggs; Kent D. Taylor; W. James Gauderman; Jerome I. Rotter; Rohit Varma; Tin Aung; Kathryn P. Burdon; Ching Yu Cheng; Jamie E. Craig; Angela J. Cree; Puya Gharahkhani; Christopher J. Hammond; Alex W. Hewitt; René Höhn; Pirro Hysi; Adriana I.Iglesias Gonzalez; Jost Jonas; Anthony Khawaja; Chiea Cheun Khor; Caroline C.W. Klaver; Francesca Pasutto; Stuart MacGregor; David Mackey; Paul Mitchell; Aniket Mishra; Calvin Pang; Louis R. Pasquale; Henriette Springelkamp; Gudmar Thorleifsson; Unnur Thorsteinsdottir; Cornelia M. van Duijn; Ananth Viswanathan; Veronique Vitart; Robert Wojciechowski; Tien Wong; Terrri L. Young; Tanja Zeller

doi:10.1093/hmg/ddw319

Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos

International Glaucoma Genetics Consortium
, Xiaoyi Gao^*
, Drew R. Nannini
, Kristen Corrao
, Mina Torres
, Yii Der I. Chen
, Bao J. Fan
, Janey L. Wiggs
, Kent D. Taylor
, W. James Gauderman
, Jerome I. Rotter
, Rohit Varma
, Tin Aung
, Kathryn P. Burdon
, Ching Yu Cheng
, Jamie E. Craig
, Angela J. Cree
, Puya Gharahkhani
, Christopher J. Hammond
, Alex W. Hewitt

René Höhn, Pirro Hysi, Adriana I.Iglesias Gonzalez, Jost Jonas, Anthony Khawaja, Chiea Cheun Khor, Caroline C.W. Klaver, Francesca Pasutto, Stuart MacGregor, David Mackey, Paul Mitchell, Aniket Mishra, Calvin Pang, Louis R. Pasquale, Henriette Springelkamp, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Cornelia M. van Duijn, Ananth Viswanathan, Veronique Vitart, Robert Wojciechowski, Tien Wong, Terrri L. Young, Tanja Zeller

^*Corresponding author for this work

University of Illinois at Chicago
Keck School of Medicine of USC
University of California at Los Angeles
Harvard University
Singapore Eye Research Institute
MOH Holdings Pte Ltd.
Menzies Institute for Medical Research
Flinders University
University of Southampton
Queensland Institute of Medical Research
St. Thomas’ Hospital Campus
University of Melbourne
University Medical Center Mainz
Erasmus University Rotterdam
Heidelberg University
University of Cambridge
Moorfields Eye Hospital NHS Foundation Trust
Genome Institute of Singapore
Friedrich-Alexander University Erlangen-Nürnberg
Centre for Ophthalmology and Visual Science
deCODE Genetics
The University of Sydney
Chinese University of Hong Kong
Medical Research Council Human Genetics Unit
Johns Hopkins Bloomberg School of Public Health
Wilmer Eye Institute
National Human Genome Research Institute (NHGRI)
University of Wisconsin-Madison
University of Hamburg

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

34 Citations (Scopus)

Abstract

The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (~730K markers) or the Illumina Hispanic/SOL BeadChip (~2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P=6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1 and ZNF469 (P < 1.25E-3). These findings provide further insight into the genetic architecture of CCT and illustrate that the use of minority groups in GWAS will help identify additional loci.

Original language	English
Pages (from-to)	5035-5045
Number of pages	11
Journal	Human Molecular Genetics
Volume	25
Issue number	22
DOIs	https://doi.org/10.1093/hmg/ddw319
Publication status	Published - 15 Nov 2016

Bibliographical note

Funding Information:
The authors would like to thank the study participants from LALES and the staff who aided in data collection and processing. This work was supported in part by National Institutes of Health (NIH; Bethesda, MD, USA) grants R01EY022651 (to XG), U10EY011753 (to RV), P30EY001792 (departmental core grant), and a grant from Midwest Eye-Banks (to XG). The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences (CTSI) grant UL1TR000124, NIDDK Diabetes Research Center (DRC) Grant DK063491 to the Southern California Diabetes Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Publisher Copyright:
© The Author 2016. Published by Oxford University Press. All rights reserved.

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10.1093/hmg/ddw319

Cite this

International Glaucoma Genetics Consortium, Gao, X., Nannini, D. R., Corrao, K., Torres, M., Chen, Y. D. I., Fan, B. J., Wiggs, J. L., Taylor, K. D., Gauderman, W. J., Rotter, J. I., Varma, R., Aung, T., Burdon, K. P., Cheng, C. Y., Craig, J. E., Cree, A. J., Gharahkhani, P., Hammond, C. J., ... Zeller, T. (2016). Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos. Human Molecular Genetics, 25(22), 5035-5045. https://doi.org/10.1093/hmg/ddw319

@article{7b5dae1159c943229a087ebd0f69df2f,

title = "Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos",

abstract = "The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (\textasciitilde{}730K markers) or the Illumina Hispanic/SOL BeadChip (\textasciitilde{}2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P=6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1 and ZNF469 (P < 1.25E-3). These findings provide further insight into the genetic architecture of CCT and illustrate that the use of minority groups in GWAS will help identify additional loci.",

author = "\{International Glaucoma Genetics Consortium\} and Xiaoyi Gao and Nannini, \{Drew R.\} and Kristen Corrao and Mina Torres and Chen, \{Yii Der I.\} and Fan, \{Bao J.\} and Wiggs, \{Janey L.\} and Taylor, \{Kent D.\} and Gauderman, \{W. James\} and Rotter, \{Jerome I.\} and Rohit Varma and Tin Aung and Burdon, \{Kathryn P.\} and Cheng, \{Ching Yu\} and Craig, \{Jamie E.\} and Cree, \{Angela J.\} and Puya Gharahkhani and Hammond, \{Christopher J.\} and Hewitt, \{Alex W.\} and Ren{\'e} H{\"o}hn and Pirro Hysi and Gonzalez, \{Adriana I.Iglesias\} and Jost Jonas and Anthony Khawaja and Khor, \{Chiea Cheun\} and Klaver, \{Caroline C.W.\} and Francesca Pasutto and Stuart MacGregor and David Mackey and Paul Mitchell and Aniket Mishra and Calvin Pang and Pasquale, \{Louis R.\} and Henriette Springelkamp and Gudmar Thorleifsson and Unnur Thorsteinsdottir and \{van Duijn\}, \{Cornelia M.\} and Ananth Viswanathan and Veronique Vitart and Robert Wojciechowski and Tien Wong and Young, \{Terrri L.\} and Tanja Zeller",

note = "Funding Information: The authors would like to thank the study participants from LALES and the staff who aided in data collection and processing. This work was supported in part by National Institutes of Health (NIH; Bethesda, MD, USA) grants R01EY022651 (to XG), U10EY011753 (to RV), P30EY001792 (departmental core grant), and a grant from Midwest Eye-Banks (to XG). The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences (CTSI) grant UL1TR000124, NIDDK Diabetes Research Center (DRC) Grant DK063491 to the Southern California Diabetes Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: {\textcopyright} The Author 2016. Published by Oxford University Press. All rights reserved.",

year = "2016",

month = nov,

day = "15",

doi = "10.1093/hmg/ddw319",

language = "English",

volume = "25",

pages = "5035--5045",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "22",

}

International Glaucoma Genetics Consortium, Gao, X, Nannini, DR, Corrao, K, Torres, M, Chen, YDI, Fan, BJ, Wiggs, JL, Taylor, KD, Gauderman, WJ, Rotter, JI, Varma, R, Aung, T, Burdon, KP, Cheng, CY, Craig, JE, Cree, AJ, Gharahkhani, P, Hammond, CJ, Hewitt, AW, Höhn, R, Hysi, P, Gonzalez, AII, Jonas, J, Khawaja, A, Khor, CC, Klaver, CCW, Pasutto, F, MacGregor, S, Mackey, D, Mitchell, P, Mishra, A, Pang, C, Pasquale, LR, Springelkamp, H, Thorleifsson, G, Thorsteinsdottir, U, van Duijn, CM, Viswanathan, A, Vitart, V, Wojciechowski, R, Wong, T, Young, TL & Zeller, T 2016, 'Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos', Human Molecular Genetics, vol. 25, no. 22, pp. 5035-5045. https://doi.org/10.1093/hmg/ddw319

TY - JOUR

T1 - Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos

AU - International Glaucoma Genetics Consortium

AU - Gao, Xiaoyi

AU - Nannini, Drew R.

AU - Corrao, Kristen

AU - Torres, Mina

AU - Chen, Yii Der I.

AU - Fan, Bao J.

AU - Wiggs, Janey L.

AU - Taylor, Kent D.

AU - Gauderman, W. James

AU - Rotter, Jerome I.

AU - Varma, Rohit

AU - Aung, Tin

AU - Burdon, Kathryn P.

AU - Cheng, Ching Yu

AU - Craig, Jamie E.

AU - Cree, Angela J.

AU - Gharahkhani, Puya

AU - Hammond, Christopher J.

AU - Hewitt, Alex W.

AU - Höhn, René

AU - Hysi, Pirro

AU - Gonzalez, Adriana I.Iglesias

AU - Jonas, Jost

AU - Khawaja, Anthony

AU - Khor, Chiea Cheun

AU - Klaver, Caroline C.W.

AU - Pasutto, Francesca

AU - MacGregor, Stuart

AU - Mackey, David

AU - Mitchell, Paul

AU - Mishra, Aniket

AU - Pang, Calvin

AU - Pasquale, Louis R.

AU - Springelkamp, Henriette

AU - Thorleifsson, Gudmar

AU - Thorsteinsdottir, Unnur

AU - van Duijn, Cornelia M.

AU - Viswanathan, Ananth

AU - Vitart, Veronique

AU - Wojciechowski, Robert

AU - Wong, Tien

AU - Young, Terrri L.

AU - Zeller, Tanja

N1 - Funding Information: The authors would like to thank the study participants from LALES and the staff who aided in data collection and processing. This work was supported in part by National Institutes of Health (NIH; Bethesda, MD, USA) grants R01EY022651 (to XG), U10EY011753 (to RV), P30EY001792 (departmental core grant), and a grant from Midwest Eye-Banks (to XG). The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences (CTSI) grant UL1TR000124, NIDDK Diabetes Research Center (DRC) Grant DK063491 to the Southern California Diabetes Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Publisher Copyright: © The Author 2016. Published by Oxford University Press. All rights reserved.

PY - 2016/11/15

Y1 - 2016/11/15

N2 - The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (~730K markers) or the Illumina Hispanic/SOL BeadChip (~2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P=6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1 and ZNF469 (P < 1.25E-3). These findings provide further insight into the genetic architecture of CCT and illustrate that the use of minority groups in GWAS will help identify additional loci.

AB - The cornea is the outermost layer of the eye and is a vital component of focusing incoming light on the retina. Central corneal thickness (CCT) is now recognized to have a significant role in ocular health and is a risk factor for various ocular diseases, such as keratoconus and primary open angle glaucoma. Most previous genetic studies utilized European and Asian subjects to identify genetic loci associated with CCT. Minority populations, such as Latinos, may aid in identifying additional loci and improve our understanding of the genetic architecture of CCT. In this study, we conducted a genome-wide association study (GWAS) in Latinos, a traditionally understudied population in genetic research, to further identify loci contributing to CCT. Study participants were genotyped using either the Illumina OmniExpress BeadChip (~730K markers) or the Illumina Hispanic/SOL BeadChip (~2.5 million markers). All study participants were 40 years of age and older. We assessed the association between individual single nucleotide polymorphisms (SNPs) and CCT using linear regression, adjusting for age, gender and principal components of genetic ancestry. To expand genomic coverage and to interrogate additional SNPs, we imputed SNPs from the 1000 Genomes Project reference panels. We identified a novel SNP, rs10453441 (P=6.01E-09), in an intron of WNT7B that is associated with CCT. Furthermore, WNT7B is expressed in the human cornea. We also replicated 11 previously reported loci, including IBTK, RXRA-COL5A1, COL5A1, FOXO1, LRRK1 and ZNF469 (P < 1.25E-3). These findings provide further insight into the genetic architecture of CCT and illustrate that the use of minority groups in GWAS will help identify additional loci.

UR - https://www.scopus.com/pages/publications/85015784914

U2 - 10.1093/hmg/ddw319

DO - 10.1093/hmg/ddw319

M3 - Article

C2 - 28171582

AN - SCOPUS:85015784914

SN - 0964-6906

VL - 25

SP - 5035

EP - 5045

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 22

ER -

Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos

Abstract

Bibliographical note

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