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Genome-Wide Linkage Analyses to Identify Loci for Diabetic Retinopathy

¹ Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona
² National Eye Institute, Bethesda, Maryland
³ Department of Ophthalmology, University of Wisconsin, Madison, Wisconsin

Address correspondence to Robert L. Hanson, PECRB, 1550 E. Indian School Rd., Phoenix, AZ 85014. E-mail: rhanson{at}mail.nih.gov

Abbreviations: ACIBD, identity by descent; LOD, logarithm of odds; PADI, peptidyl arginine deiminase; WESDR, Wisconsin Epidemiology of Diabetic Retinopathy

Hyperglycemia and long duration of diabetes are widely recognized risk factors for diabetic retinopathy, but inherited susceptibility may also play a role because retinopathy aggregates in families. A genome-wide linkage analysis was conducted in 211 sibships in which 2 siblings had diabetes and retinal photographs were available from a longitudinal study. These sibships were a subset of 322 sibships who had participated in a previous linkage study of diabetes and related traits; they comprised 607 diabetic individuals in 725 sibpairs. Retinal photographs were graded for presence and severity of diabetic retinopathy according to a modification of the Airlie House classification system. The grade for the worse eye was adjusted for age, sex, and diabetes duration and analyzed as a quantitative trait. Heritability of diabetic retinopathy in this group was 18% (95% CI 2–36). A genome-wide linkage analysis using variance components modeling found evidence of linkage on chromosome 1p. Using single-point analysis, the peak logarithm of odds (LOD) was 3.1 for marker D1S3669 (34.2 cM), whereas with multipoint analysis the peak LOD was 2.58 at 35 cM. No other areas of suggestive linkage were found. We propose that an area on chromosome 1 may harbor a gene or genes conferring susceptibility to diabetic retinopathy.

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