Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos.
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.
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.
Xiaoyi
X
Gao
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.
Drew R
DR
Nannini
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA.
Kristen
K
Corrao
USC Roski Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, CA, USA.
Mina
M
Torres
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics and Medicine at Harbor-UCLA, Torrance, CA, USA.
Yii-Der I
YI
Chen
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
Bao J
BJ
Fan
Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA 02114, USA.
Janey L
JL
Wiggs
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics and Medicine at Harbor-UCLA, Torrance, CA, USA.
Kent D
KD
Taylor
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
W James
WJ
Gauderman
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics and Medicine at Harbor-UCLA, Torrance, CA, USA.
Jerome I
JI
Rotter
USC Roski Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, CA, USA.
Rohit
R
Varma
D000328:Adult; D000368:Aged; D003315:Cornea / Q000473:pathology* / Q000502:physiology; D063171:Corneal Pachymetry / Q000379:methods; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D005901:Glaucoma / Q000235:genetics; D005902:Glaucoma, Open-Angle / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007640:Keratoconus / Q000235:genetics; D015141:Los Angeles; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism
C490675:WNT7B protein, human; D051153:Wnt Proteins