April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Genome Wide Association for Diabetic Retinopathy in Mexican Americans: The Family Investigation of Nephropathy and Diabetes (FIND) Study
Author Affiliations & Notes
  • Kent D. Taylor
    Medical Genetics, Cedars-Sinai Medical Center, Los Angeles, California
  • Emily Y. Chew
    Epidemiology & Clinical Applications, National Eye Inst/NIH, Bethesda, Maryland
  • Sharon Adler
    Nephrology and Hypertension, University of California Los Angeles, Los Angeles, California
  • Fenghua Deng
    Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, Ohio
  • Matthew D. Davis
    Ophthalmology & Visual Sciences,
    Univ of Wisconsin-Madison, Madison, Wisconsin
  • Ronald P. Danis
    Ophthal & Vis Sciences,
    Univ of Wisconsin-Madison, Madison, Wisconsin
  • Nedal Arar
    Medicine, University of Texas, San Antonio, Texas
  • Xiuqing Guo
    Medical Genetics, Cedars-Sinai Medical Center, Los Angeles, California
  • Sudha K. Iyengar
    Epidemiology & Biostatistics, Case Western Reserve University, Cleveland, Ohio
  • Find Consortium
    Medical Genetics, Cedars-Sinai Medical Center, Los Angeles, California
  • Footnotes
    Commercial Relationships  Kent D. Taylor, None; Emily Y. Chew, None; Sharon Adler, None; Fenghua Deng, None; Matthew D. Davis, None; Ronald P. Danis, None; Nedal Arar, None; Xiuqing Guo, None; Sudha K. Iyengar, None
  • Footnotes
    Support  NIDDK grant U01DK057292
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 4819. doi:
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      Kent D. Taylor, Emily Y. Chew, Sharon Adler, Fenghua Deng, Matthew D. Davis, Ronald P. Danis, Nedal Arar, Xiuqing Guo, Sudha K. Iyengar, Find Consortium; Genome Wide Association for Diabetic Retinopathy in Mexican Americans: The Family Investigation of Nephropathy and Diabetes (FIND) Study. Invest. Ophthalmol. Vis. Sci. 2011;52(14):4819.

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Abstract

Purpose: : Diabetic Retinopathy (DR) is a leading cause of blindness among those with either type 1 or type 2 diabetes mellitus (DM). Mexican Americans have an increased burden of diabetes and its complications, and show high heritability for severe DR. To identify novel loci that show association with DR, we conducted a genome-wide association study (GWAS) in a subset of Mexican American samples that also underwent a GWAS for type 2 diabetic nephropathy (DN).

Methods: : The FIND participants had ophthalmological exams and stereoscopic seven-field retinal photos that were graded according to the methods of the Early Treatment Diabetic Retinopathy Study Group (ETDRS). Genotyping was performed using the Affymetrix 6.0 chip. Cases with any DR (N=238) were contrasted with controls (N = 1162) who were disease free at the time of study visit. Logistic regression methods were used for genetic contrasts, adjusting for the effects of sex, study center, DM duration, and two principal components for population structure. Glycosylated hemoglobin (HbA1C) was also examined, but was not significant, and hence not retained in the final model.

Results: : After GWAS analysis, no markers reached genome-wide significance of p = 10-8 in our sample, but a number of markers with p-values between 10-5 and 10-7 were observed. The best p-value was on chromosome 3 at rs11713025 (Odds Ratio = 1.7; p = 7 x 10-7) between the carbohydrate sulfotransferase gene, CHST2, and an unknown transcript, LOC10013-605. The CHST2 moiety is expressed in vascular endothelial cells, and may contribute to generation of L-selectin ligand production under inflammatory stress.

Conclusions: : We have conducted a GWAS for DR in Mexican Americans and have identified several interesting signals that warrant follow-up. Our goal is to replicate our findings in additional Mexican American samples, and determine if these loci show portability across other ethnic groups in FIND, including European Americans, American Indians and African Americans.

Keywords: diabetic retinopathy • genetics • clinical (human) or epidemiologic studies: outcomes/complications 
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