title: A genome-wide association study of central corneal thickness in Latinos.
abstract: OBJECTIVE
  Central corneal thickness (CCT) is a clinically important risk factor for primary open-angle glaucoma and keratoconus. Genetic factors controlling CCT in Latinos, the most populous minority population in the United States, are unclear. Here we describe the first genome-wide association study (GWAS) report of CCT in Latinos.
  
  
  METHODS
  We performed a GWAS for CCT on 1768 Latinos recruited in the Los Angeles Latino Eye Study (LALES) using Illumina's HumanOmniExpress BeadChip (∼730K markers). To discover additional associated single-nucleotide polymorphisms (SNPs), we imputed SNPs based on the 1000 Genomes Project reference panels. All subjects were 40 years of age and older. We used linear regression with adjustment for age, sex, and principal components of genetic ancestry.
  
  
  RESULTS
  we replicated the involvement of several previously reported loci, SUCH AS RXRA-COL5A1, FOXO1, and ZNF469, for CCT in Latinos (P 0.002). moreover, we discovered novel SNPS, RS3118515, RS943423, RS3118594, AND RS3132307, THAT REACHED GWAS SIGNIFICANCE (P 5 10(8)) in the uncharacterized LOC100506532 (GENE TYPE: miscRNA) for CCT in Latinos. By conditional analysis, we demonstrate that rs3118515 in this gene is responsible for the GWAS signal in the chromosome 9 RXRA-COL5A1 region in Latinos. Moreover, multiple sources of ENCODE evidence suggest that rs3118515 is in a regulatory region. Reverse-transcription PCR products indicated that transcripts of LOC100506532 surrounding rs3118515 were expressed in human corneas.
  
  
  CONCLUSIONS
  We discovered novel SNPs for CCT in Latinos and provided the first reported evidence of the corneal expression of LOC100506532. These results help to further increase our understanding of the genetic architecture of CCT.
authors.affiliation: Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.rgao@uic.edu
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Gao
authors.forename: W James
authors.initials: WJ
authors.lastname: Gauderman
authors.forename: Yutao
authors.initials: Y
authors.lastname: Liu
authors.forename: Paul
authors.initials: P
authors.lastname: Marjoram
authors.forename: Mina
authors.initials: M
authors.lastname: Torres
authors.forename: Talin
authors.initials: T
authors.lastname: Haritunians
authors.forename: Jane Z
authors.initials: JZ
authors.lastname: Kuo
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
authors.forename: R Rand
authors.initials: RR
authors.lastname: Allingham
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hauser
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Rohit
authors.initials: R
authors.lastname: Varma
mesh_terms: D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D024062:Collagen Type V / Q000235:genetics; D003315:Cornea / Q000033:anatomy & histology*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D015141:Los Angeles; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D047490:Retinoid X Receptor alpha / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics
chemical_list: C530725:COL5A1 protein, human; D024062:Collagen Type V; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D047490:Retinoid X Receptor alpha; D014157:Transcription Factors; C530065:ZNF469 protein, human