TY - JOUR
T1 - Genome-wide association study identifies WNT7B as a novel locus for central corneal thickness in Latinos
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 - International Glaucoma Genetics Consortium
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
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.
KW - Cornea central thickness
KW - Genome-wide association study
KW - Latinos
KW - WNT7B
KW - International Glaucoma Genetics Consortium
UR - http://www.scopus.com/inward/record.url?scp=85015784914&partnerID=8YFLogxK
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 -