title: A Genome-Wide Association Study of Vertical Cup-Disc Ratio in a Latino Population.
abstract: Vertical cup-disc ratio (VCDR) is used as a clinical assessment measure to identify and monitor glaucomatous damage to the optic nerve. Previous genetic studies conducted in European and Asian populations have identified many loci associated with VCDR. The genetic factors in other ethnic populations, such as Latino, influencing VCDR remain to be determined. Here, we describe the first genome-wide association study (GWAS) on VCDR in Latino individuals.
  
  
  
  We conducted this GWAS on VCDR using 4537 Latino individuals who were genotyped by using either the Illumina OmniExpress BeadChip (∼730K markers) or the Illumina Hispanic/SOL BeadChip (∼2.5 million markers). Study subjects were 40 years of age and older. Linear regression, adjusting for age, sex, and principal components of genetic ancestry, was conducted to assess the associations between single nucleotide polymorphisms (SNPs) and VCDR. We imputed SNPs from the 1000 Genomes Project to integrate additional SNPs not directly genotyped.
  
  
  
  We replicated two previously reported SNPs that reached GWAS significance, rs1900005 and rs7916697, in the ATOH7-PBLD region, as well as identified two suggestive associations in the CDC7-TGFBR3 region on chromosome 1p22.1 and in the ZNF770-DPH6 region on chromosome 15q14. We discovered a novel SNP, rs56238729 (P = 1.22 × 10-13), in the ATOH7-PBLD region that is significantly associated with VCDR in Latino individuals. We replicated eight previously reported regions, including COL8A1, CDKN2B-CDKN2BAS, BMP2, and CHEK2 (P < 2.17 × 10-3).
  
  
  
  Our results discovered a novel SNP that is significantly associated with VCDR in Latino individuals and confirmed previously reported loci, providing further insight into the genetic architecture of VCDR.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States.
authors.forename: Drew R
authors.initials: DR
authors.lastname: Nannini
authors.affiliation: USC Roski Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, California, United States.
authors.forename: Mina
authors.initials: M
authors.lastname: Torres
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics and Medicine at Harbor-UCLA, Torrance, California, United States.
authors.forename: Yii-Der I
authors.initials: YI
authors.lastname: Chen
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics and Medicine at Harbor-UCLA, Torrance, California, United States.
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.affiliation: Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics and Medicine at Harbor-UCLA, Torrance, California, United States.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: USC Roski Eye Institute, Department of Ophthalmology, University of Southern California, Los Angeles, California, United States.
authors.forename: Rohit
authors.initials: R
authors.lastname: Varma
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois, United States.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Gao
mesh_terms: D000328:Adult; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002140:California / Q000453:epidemiology; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D005901:Glaucoma / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs; D006630:Hispanic or Latino; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009898:Optic Disk / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C456975:ATOH7 protein, human