Genome-wide association study identifiesWNT7Bas 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 (~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.3

Omics Biomarkers in Ophthalmology

“…94,[96][97][98][99][100][101]. With these studies, genetic factors involved in IOP, disc area, vertical cup-disc ratio, cup area, anterior chamber depth, and central corneal thickness have been identified, which are potentially relevant for glaucoma development.…”

Molecular Genetics of Keratoconus: Clinical Implications

“…In totally 15,168 study samples that included Japanese, Chinese or European ethicity, rs10453441 in WNT7B was strongly associated with both CC and axial length [91]. WNT7B rs10453441 is the only SNP associated with both traits of CCT and CC [92]. While these SNPs have no consistent and strong association with keratoconus, an exome sequencing analysis identified a WNT10A variant that was associated with corneal thickness and keratoconus [93].…”

A genome‐wide association study of prostate cancer in Latinos

“…Latinos are extensively admixed from multiple ancestries including Amerindian (AMR), European (EUR) and African (AFR), 6 with large variation in ancestry proportions observed across subgroups and individuals. For example, GWAS in Latinos of phenotypes such as central corneal thickness, 8 asthma 9 and diabetes, 10 have discovered novel susceptibility not reported in other populations. Throughout the Americas, and even within a single country, AMR ancestry proportions vary widely.…”

“…6,7 GWAS in non-European populations have provided insight into ancestry-specific variation and have revealed regions of susceptibility that are of particular importance in certain populations. For example, GWAS in Latinos of phenotypes such as central corneal thickness, 8 asthma 9 and diabetes, 10 have discovered novel susceptibility not reported in other populations. For breast cancer, an admixture-mapping study discovered higher AMR ancestry at chromosome 6q25 and protective variants within this region 11 that are only found in AMR populations.…”