A genome-wide association study of central corneal thickness in Latinos

Xiaoyi Gao, W. James Gauderman, Yutao Liu, Paul Marjoram, Mina Torres, Talin Haritunians, Jane Z. Kuo, Yii Der I. Chen, R. Rand Allingham, Michael A. Hauser, Kent D. Taylor, Jerome I. Rotter, Rohit Varma

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

PURPOSE. Central corneal thickness (CCT) is a clinically important risk factor for primary openangle 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 RXRACOL5A1, 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.

Original languageEnglish (US)
Pages (from-to)2435-2443
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume54
Issue number4
DOIs
StatePublished - Apr 12 2013
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Hispanic Americans
Single Nucleotide Polymorphism
Keratoconus
Chromosomes, Human, Pair 9
Los Angeles
Nucleic Acid Regulatory Sequences
Glaucoma
Cornea
Genes
Reverse Transcription
Linear Models
Genome
Polymerase Chain Reaction
Population

Keywords

  • Central corneal thickness
  • GWAS
  • Latino
  • rs3118515, LOC100506532

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Gao, X., Gauderman, W. J., Liu, Y., Marjoram, P., Torres, M., Haritunians, T., ... Varma, R. (2013). A genome-wide association study of central corneal thickness in Latinos. Investigative Ophthalmology and Visual Science, 54(4), 2435-2443. https://doi.org/10.1167/iovs.13-11692

A genome-wide association study of central corneal thickness in Latinos. / Gao, Xiaoyi; Gauderman, W. James; Liu, Yutao; Marjoram, Paul; Torres, Mina; Haritunians, Talin; Kuo, Jane Z.; Chen, Yii Der I.; Allingham, R. Rand; Hauser, Michael A.; Taylor, Kent D.; Rotter, Jerome I.; Varma, Rohit.

In: Investigative Ophthalmology and Visual Science, Vol. 54, No. 4, 12.04.2013, p. 2435-2443.

Research output: Contribution to journalArticle

Gao, X, Gauderman, WJ, Liu, Y, Marjoram, P, Torres, M, Haritunians, T, Kuo, JZ, Chen, YDI, Allingham, RR, Hauser, MA, Taylor, KD, Rotter, JI & Varma, R 2013, 'A genome-wide association study of central corneal thickness in Latinos', Investigative Ophthalmology and Visual Science, vol. 54, no. 4, pp. 2435-2443. https://doi.org/10.1167/iovs.13-11692
Gao, Xiaoyi ; Gauderman, W. James ; Liu, Yutao ; Marjoram, Paul ; Torres, Mina ; Haritunians, Talin ; Kuo, Jane Z. ; Chen, Yii Der I. ; Allingham, R. Rand ; Hauser, Michael A. ; Taylor, Kent D. ; Rotter, Jerome I. ; Varma, Rohit. / A genome-wide association study of central corneal thickness in Latinos. In: Investigative Ophthalmology and Visual Science. 2013 ; Vol. 54, No. 4. pp. 2435-2443.
@article{b8640ca15af64b5686dd42b2b4bcc9f8,
title = "A genome-wide association study of central corneal thickness in Latinos",
abstract = "PURPOSE. Central corneal thickness (CCT) is a clinically important risk factor for primary openangle 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 RXRACOL5A1, 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.",
keywords = "Central corneal thickness, GWAS, Latino, rs3118515, LOC100506532",
author = "Xiaoyi Gao and Gauderman, {W. James} and Yutao Liu and Paul Marjoram and Mina Torres and Talin Haritunians and Kuo, {Jane Z.} and Chen, {Yii Der I.} and Allingham, {R. Rand} and Hauser, {Michael A.} and Taylor, {Kent D.} and Rotter, {Jerome I.} and Rohit Varma",
year = "2013",
month = "4",
day = "12",
doi = "10.1167/iovs.13-11692",
language = "English (US)",
volume = "54",
pages = "2435--2443",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "4",

}

TY - JOUR

T1 - A genome-wide association study of central corneal thickness in Latinos

AU - Gao, Xiaoyi

AU - Gauderman, W. James

AU - Liu, Yutao

AU - Marjoram, Paul

AU - Torres, Mina

AU - Haritunians, Talin

AU - Kuo, Jane Z.

AU - Chen, Yii Der I.

AU - Allingham, R. Rand

AU - Hauser, Michael A.

AU - Taylor, Kent D.

AU - Rotter, Jerome I.

AU - Varma, Rohit

PY - 2013/4/12

Y1 - 2013/4/12

N2 - PURPOSE. Central corneal thickness (CCT) is a clinically important risk factor for primary openangle 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 RXRACOL5A1, 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.

AB - PURPOSE. Central corneal thickness (CCT) is a clinically important risk factor for primary openangle 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 RXRACOL5A1, 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.

KW - Central corneal thickness

KW - GWAS

KW - Latino

KW - rs3118515, LOC100506532

UR - http://www.scopus.com/inward/record.url?scp=84875964330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875964330&partnerID=8YFLogxK

U2 - 10.1167/iovs.13-11692

DO - 10.1167/iovs.13-11692

M3 - Article

C2 - 23493294

AN - SCOPUS:84875964330

VL - 54

SP - 2435

EP - 2443

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 4

ER -