Arti Tandon1, Ching J Chen2, Alan Penman3, Heather Hancock2, Maurice James4, Deeba Husain5, Christopher Andreoli6, Xiaohui Li7, Jane Z Kuo8, Omolola Idowu2, Daniel Riche9, Evangelia Papavasilieou5, Stacey Brauner5, Sataria O Smith2, Suzanne Hoadley2, Cole Richardson2, Troy Kieser6, Vanessa Vazquez10, Cheryl Chi10, Marlene Fernandez11, Maegan Harden12, Mary Frances Cotch13, David Siscovick14, Herman A Taylor9, James G Wilson9, David Reich1, Tien Y Wong15, Ronald Klein16, Barbara E K Klein16, Jerome I Rotter7, Nick Patterson17, Lucia Sobrin5. 1. Department of Genetics Harvard Medical School, Boston, Massachusetts, United States 2Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States. 2. Department of Ophthalmology, University of Mississippi Medical Center, Jackson, Mississippi, United States. 3. Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States 5Department of Biostatistics, University of Mississippi Medical Center, Jackson, Mississippi, United States. 4. Ophthalmology, St Dominic's Hospital, Jackson, Mississippi, United States. 5. Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States. 6. Visual Services Department, Harvard Vanguard Medical Associates, Boston, Massachusetts, United States. 7. Institute for Translational Genomics and Population Sciences, LABiomed and Department of Pediatrics, Harbor-UCLA, Torrance, California, United States. 8. Institute for Translational Genomics and Population Sciences, LABiomed and Department of Pediatrics, Harbor-UCLA, Torrance, California, United States 10Pathway Genomic Corporation, San Diego, California, United States. 9. Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States. 10. Department of Ophthalmology, Boston Medical Center, Boston, Massachusetts, United States. 11. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States. 12. Genomics Platform, Broad Institute, Cambridge, Massachusetts, United States. 13. Division of Epidemiology and Clinical Applications, National Eye Institute, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, United States. 14. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States. 15. Office of Clinical Sciences, Duke-NUS Graduate Medical School, National University of Singapore, Singapore 17Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. 16. Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States. 17. Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States.
Abstract
PURPOSE: To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). METHODS: Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. RESULTS: In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16-1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59-2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. CONCLUSIONS: In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present.
PURPOSE: To examine the relationship between proportion of African ancestry (PAA) and proliferative diabetic retinopathy (PDR) and to identify genetic loci associated with PDR using admixture mapping in African Americans with type 2 diabetes (T2D). METHODS: Between 1993 and 2013, 1440 participants enrolled in four different studies had fundus photographs graded using the Early Treatment Diabetic Retinopathy Study scale. Cases (n = 305) had PDR while controls (n = 1135) had nonproliferative diabetic retinopathy (DR) or no DR. Covariates included diabetes duration, hemoglobin A1C, systolic blood pressure, income, and education. Genotyping was performed on the Affymetrix platform. The association between PAA and PDR was evaluated using logistic regression. Genome-wide admixture scanning was performed using ANCESTRYMAP software. RESULTS: In the univariate analysis, PDR was associated with increased PAA (odds ratio [OR] = 1.36, 95% confidence interval [CI] = 1.16-1.59, P = 0.0002). In multivariate regression adjusting for traditional DR risk factors, income and education, the association between PAA and PDR was attenuated and no longer significant (OR = 1.21, 95% CI = 0.59-2.47, P = 0.61). For the admixture analyses, the maximum genome-wide score was 1.44 on chromosome 1. CONCLUSIONS: In this largest study of PDR in African Americans with T2D to date, an association between PAA and PDR is not present after adjustment for clinical, demographic, and socioeconomic factors. No genome-wide significant locus (defined as having a locus-genome statistic > 5) was identified with admixture analysis. Further analyses with even larger sample sizes are needed to definitively assess if any admixture signal for DR is present.
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