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A Genome-Wide Linkage Scan for Diabetic Retinopathy Susceptibility Genes in Mexican Americans With Type 2 Diabetes From Starr County, Texas

¹ Human Genetics Center, University of Texas Health Science Center at Houston School of Public Health, Houston, Texas
² Valley Retina Institute, McAllen, Texas
³ Department of Ophthalmology and Visual Sciences, University of Wisconsin–Madison Medical School, Madison, Wisconsin

Address correspondence and reprint requests to Craig L. Hanis, University of Texas Health, Science Center at Houston, P.O. Box 20186, Houston, TX 77225. E-mail: craig.l.hanis{at}uth.tmc.edu

Abbreviations: LOD, logarithm of odds; OSA, ordered-subset analysis

We conducted a genome-wide linkage scan for genes contributing to retinopathy risk using 794 diabetes case subjects from 393 Mexican-American families from Starr County, Texas, having at least two diabetic siblings. The sample included 567 retinopathy case subjects comprising 282 affected sibling pairs. Retinopathy was classified as none, early nonproliferative, moderate-to-severe nonproliferative, or proliferative. Using 360 polymorphic markers (average spacing 9.4 cM), we conducted nonparametric linkage analysis followed by ordered-subset analysis (OSA) ranking families by average age of diabetes diagnosis. For any retinopathy, the highest LOD scores including all families were on chromosomes 3 (2.41 at 117 cM) and 12 (2.47 at 15.5). OSA logarithm of odds (LOD) scores >2 for any retinopathy occurred on chromosomes 12 (4.47 at 13.2 cM), 15 (3.65 at 100.6), and 20 (2.67 at 54.1). Scores >2 for either moderate-to-severe nonproliferative or proliferative retinopathy occurred on chromosomes 5 (2.53 at 11.2 cM), 6 (2.28 at 30.6), and 19 (2.21 at 100.6). Thus, unconditional linkage analysis revealed suggestive evidence of linkage with retinopathy on two chromosomes, whereas OSA revealed strong evidence of linkage on two chromosomes, and suggestive evidence on four. Candidate genes were identified in most implicated regions.

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