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

Xiaoyi Gao, Drew R. Nannini, Kristen Corrao, Mina Torres, Yii Der Ida 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 HöhnPirro G. Hysi, Adriana I Iglesias Gonzalez, Jost B. 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 Y. Wong, Terrri L. Young, Tanja Zeller, International Glaucoma Genetics Consortium

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)


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 languageEnglish
Pages (from-to)5035-5045
Number of pages11
JournalHuman Molecular Genetics
Issue number22
Publication statusPublished - 15 Nov 2016


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