March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Evidence For Association Between COL5A1 SNPs Associated With Central Corneal Thickness And Keratoconus
Author Affiliations & Notes
  • Xiaohui Li
    Medical Genetics Institute, Ophthalmology & Visual Sciences,
    Cedars-Sinai Medical Center, Los Angeles, California
  • Yelena Bykhovskaya
    Regenerative Medicine Institute, Epidemiology & Biostatistics,
    Cedars-Sinai Medical Center, Los Angeles, California
  • Talin Haritunians
    Medical Genetics Institute, Ophthalmology & Visual Sciences,
    Cedars-Sinai Medical Center, Los Angeles, California
  • David Siscovick
    University of Washington, Seattle, Washington
  • Anthony J. Aldave
    Cornea Service, UCLA, Los Angeles, California
  • Loretta B. Szczotka-Flynn
    Medical Genetics Institute, Ophthalmology & Visual Sciences,
    Case Western Reserve University, Cleveland, Ohio
  • Sudha K. Iyengar
    Regenerative Medicine Institute, Epidemiology & Biostatistics,
    Case Western Reserve University, Cleveland, Ohio
  • Jerome I. Rotter
    Medical Genetics Institute, Ophthalmology & Visual Sciences,
    Cedars-Sinai Medical Center, Los Angeles, California
  • Kent D. Taylor
    Medical Genetics Institute, Ophthalmology & Visual Sciences,
    Cedars-Sinai Medical Center, Los Angeles, California
  • Yaron S. Rabinowitz
    Regenerative Medicine Institute, Epidemiology & Biostatistics,
    Cedars-Sinai Medical Center, Los Angeles, California
  • Footnotes
    Commercial Relationships  Xiaohui Li, None; Yelena Bykhovskaya, None; Talin Haritunians, None; David Siscovick, None; Anthony J. Aldave, None; Loretta B. Szczotka-Flynn, None; Sudha K. Iyengar, None; Jerome I. Rotter, None; Kent D. Taylor, None; Yaron S. Rabinowitz, None
  • Footnotes
    Support  NEI 09052, NCRR M01-RR00425, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, U01 HL080295 and R01 HL087652
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 79. doi:
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      Xiaohui Li, Yelena Bykhovskaya, Talin Haritunians, David Siscovick, Anthony J. Aldave, Loretta B. Szczotka-Flynn, Sudha K. Iyengar, Jerome I. Rotter, Kent D. Taylor, Yaron S. Rabinowitz; Evidence For Association Between COL5A1 SNPs Associated With Central Corneal Thickness And Keratoconus. Invest. Ophthalmol. Vis. Sci. 2012;53(14):79.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Several genome-wide association studies (GWASs) of central corneal thickness (CCT) have identified genome-wide significant associations for single nucleotide polymorphisms (SNPs) located near or within the collagen, type V, alpha 1, gene (COL5A1), which has been mapped to 9q34.2-q34.3. Given the fact that in a previous genome-wide linkage study of keratoconus families, we identified a maximum LOD score of 2.7 at 9q34, we examined the results of association tests between this gene and keratoconus in two independent case-control cohorts and a family sample.

Methods: : GWAS was performed using Illumina 370K beadchips in a discovery panel of 222 local Caucasian keratoconus patients and 3324 controls from the Cardiovascular Health Study (CHS). Replication of positively associated SNPs was performed in an independent case-control panel (304 cases from three centers and 518 local controls) and a local family panel (186 subjects in 41 families). Logistic regression models with adjustments for principal components implemented in PLINK were used to test for association in case-control samples. Generalized estimation equation models accounting for familial correlations implemented in GWAF were used for association testing in families.

Results: : Two SNPs, located near or in COL5A1 gene, rs1536482 (OR=1.32, p=6.5×10-3) and rs7044529 (OR=1.44, p=7.4×10-3) were identified in the GWAS discovery cohort. Replication in the case-control samples confirmed association with rs1536482 (OR=1.28, p=0.02), but not with rs7044529 (OR=1.02, p=0.92). Replication in the family samples confirmed a significant association with rs7044529 (OR=1.96, p=0.03) and yielded a similar yet not significant association for rs1536482 (OR=1.27, p=0.20). The meta p values of rs1536482 and rs7044529 combining three keratoconus cohorts were 1.5×10-4 (OR=1.30) and 2.9×10-3 (OR=1.39), respectively. Interestingly, both of these SNPs have been reported to be associated with CCT: rs1536482 in Caucasian populations with a p value of 7.1×10-8 and rs7044529 in both Caucasians and Asians with a meta p of 1.0x10-8.

Conclusions: : SNPs in COL5A1, which regulate normal variation in CCT, may also play a role in the corneal thinning in keratoconus.

Keywords: keratoconus • gene mapping 
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