Heritability of the Severity of Diabetic Retinopathy: The FIND-Eye Study

Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1)...

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Published in:Investigative ophthalmology & visual science 2008-09, Vol.49 (9), p.3839-3845
Main Authors: Arar, Nedal H, Freedman, Barry I, Adler, Sharon G, Iyengar, Sudha K, Chew, Emily Y, Davis, Mathew D, Satko, Scott G, Bowden, Donald W, Duggirala, Ravi, Elston, Robert C, Guo, Xiuxing, Hanson, Robert L, Igo, Robert P., Jr, Ipp, Eli, Kimmel, Paul L, Knowler, William C, Molineros, Julio, Nelson, Robert G, Pahl, Madeleine V, Quade, Shannon R. E, Rasooly, Rebekah S, Rotter, Jerome I, Saad, Mohammed F, Scavini, Marina, Schelling, Jeffrey R, Sedor, John R, Shah, Vallabh O, Zager, Philip G, Abboud, Hanna E, on behalf of Family Investigation of Nephropathy and Diabetes Research Group
Format: Article
Language:English
Subjects:
Biological and medical sciences
Continental Population Groups
Creatinine - blood
Diabetes. Impaired glucose tolerance
Diabetic Angiopathies - physiopathology
Diabetic Nephropathies - genetics
Diabetic Nephropathies - physiopathology
Diabetic Retinopathy - diagnosis
Diabetic Retinopathy - genetics
Diabetic Retinopathy - physiopathology
Endocrine pancreas. Apud cells (diseases)
Endocrinopathies
Ethnic Groups
Etiopathogenesis. Screening. Investigations. Target tissue resistance
Eye and associated structures. Visual pathways and centers. Vision
Family
Female
Fluorescein Angiography
Fundamental and applied biological sciences. Psychology
Humans
Male
Medical sciences
Microcirculation
Ophthalmology
Phenotype
Retinopathies
Severity of Illness Index
Siblings
Vertebrates: nervous system and sense organs
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Summary:Diabetic retinopathy (DR) and diabetic nephropathy (DN) are serious microvascular complications of diabetes mellitus. Correlations between severity of DR and DN and computed heritability estimates for DR were determined in a large, multiethnic sample of diabetic families. The hypothesis was that (1) the severity of DR correlates with the presence and severity of nephropathy in individuals with diabetes mellitus, and (2) the severity of DR is under significant familial influence in members of multiplex diabetic families. The Family Investigation of Nephropathy and Diabetes (FIND) was designed to evaluate the genetic basis of DN in American Indians, European Americans, African Americans, and Mexican Americans. FIND enrolled probands with advanced DN, along with their diabetic siblings who were concordant and discordant for nephropathy. These diabetic family members were invited to participate in the FIND-Eye study to determine whether inherited factors underlie susceptibility to DR and its severity. FIND-Eye participants underwent eye examinations and had fundus photographs taken. The severity of DR was graded by using the Early Treatment Diabetic Retinopathy Study Classification (ETDRS). Sib-sib correlations were calculated with the SAGE 5.0 program FCOR, to estimate heritability of retinopathy severity. This report summarizes the results for the first 2368 diabetic subjects from 767 families enrolled in FIND-Eye; nearly 50% were Mexican American, the largest single ethnicity within FIND. The overall prevalence of DR was high; 33.4% had proliferative DR; 7.5%, 22.8%, and 9.5% had severe, moderate, and mild nonproliferative DR, respectively; 26.6% had no DR. The severity of DR was significantly associated with severity of DN, both by phenotypic category and by increasing serum creatinine concentration (chi(2) = 658.14, df = 20; P < 0.0001). The sib-sib correlation for DR severity was 0.1358 in the total sample and 0.1224 when limited to the Mexican-American sample. Broad sense heritabilities for DR were 27% overall and 24% in Mexican-American families. The polygenic heritability of liability for proliferative DR approximated 25% in this FIND-Eye sample. These data confirm that the severity of DR parallels the presence and severity of nephropathy in individuals with diabetes mellitus. The severity of DR in members of multiplex diabetic families appears to have a significant familial connection.
ISSN:0146-0404
1552-5783
1552-5783
DOI:10.1167/iovs.07-1633