title: African Ancestry Analysis and Admixture Genetic Mapping for Proliferative Diabetic Retinopathy in African Americans.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Genetics Harvard Medical School, Boston, Massachusetts, United States 2Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States.
authors.forename: Arti
authors.initials: A
authors.lastname: Tandon
authors.affiliation: Department of Ophthalmology, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: Ching J
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States 5Department of Biostatistics, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: Alan
authors.initials: A
authors.lastname: Penman
authors.affiliation: Department of Ophthalmology, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: Heather
authors.initials: H
authors.lastname: Hancock
authors.affiliation: Ophthalmology, St Dominic's Hospital, Jackson, Mississippi, United States.
authors.forename: Maurice
authors.initials: M
authors.lastname: James
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States.
authors.forename: Deeba
authors.initials: D
authors.lastname: Husain
authors.affiliation: Visual Services Department, Harvard Vanguard Medical Associates, Boston, Massachusetts, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Andreoli
authors.affiliation: Institute for Translational Genomics and Population Sciences, LABiomed and Department of Pediatrics, Harbor-UCLA, Torrance, California, United States.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Jane Z
authors.initials: JZ
authors.lastname: Kuo
authors.affiliation: Department of Ophthalmology, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: Omolola
authors.initials: O
authors.lastname: Idowu
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Riche
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Papavasilieou
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States.
authors.forename: Stacey
authors.initials: S
authors.lastname: Brauner
authors.affiliation: Department of Ophthalmology, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: Sataria O
authors.initials: SO
authors.lastname: Smith
authors.affiliation: Department of Ophthalmology, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hoadley
authors.affiliation: Department of Ophthalmology, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: Cole
authors.initials: C
authors.lastname: Richardson
authors.affiliation: Visual Services Department, Harvard Vanguard Medical Associates, Boston, Massachusetts, United States.
authors.forename: Troy
authors.initials: T
authors.lastname: Kieser
authors.affiliation: Department of Ophthalmology, Boston Medical Center, Boston, Massachusetts, United States.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Vazquez
authors.affiliation: Department of Ophthalmology, Boston Medical Center, Boston, Massachusetts, United States.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Chi
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States.
authors.forename: Marlene
authors.initials: M
authors.lastname: Fernandez
authors.affiliation: Genomics Platform, Broad Institute, Cambridge, Massachusetts, United States.
authors.forename: Maegan
authors.initials: M
authors.lastname: Harden
authors.affiliation: Division of Epidemiology and Clinical Applications, National Eye Institute, Intramural Research Program, National Institutes of Health, Bethesda, Maryland, United States.
authors.forename: Mary Frances
authors.initials: MF
authors.lastname: Cotch
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, United States.
authors.forename: David
authors.initials: D
authors.lastname: Siscovick
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: Herman A
authors.initials: HA
authors.lastname: Taylor
authors.affiliation: Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, United States.
authors.forename: James G
authors.initials: JG
authors.lastname: Wilson
authors.affiliation: Department of Genetics Harvard Medical School, Boston, Massachusetts, United States 2Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States.
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.affiliation: Office of Clinical Sciences, Duke-NUS Graduate Medical School, National University of Singapore, Singapore 17Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
authors.forename: Tien Y
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Ronald
authors.initials: R
authors.lastname: Klein
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, United States.
authors.forename: Barbara E K
authors.initials: BE
authors.lastname: Klein
authors.affiliation: Institute for Translational Genomics and Population Sciences, LABiomed and Department of Pediatrics, Harbor-UCLA, Torrance, California, United States.
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.affiliation: Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, United States.
authors.forename: Nick
authors.initials: N
authors.lastname: Patterson
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States.
authors.forename: Lucia
authors.initials: L
authors.lastname: Sobrin
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics* / Q000706:statistics & numerical data; D000368:Aged; D001794:Blood Pressure / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D003930:Diabetic Retinopathy / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012044:Regression Analysis; D012307:Risk Factors
chemical_list: D006442:Glycated Hemoglobin