Heritability of the severity of diabetic retinopathy: the FIND-Eye study.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Arar
Nedal H
NH
Family Investigation of Nephropathy and Diabetes (FIND) Genetic Analysis and Data Coordinating Center, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA.
Freedman
Barry I
BI
Adler
Sharon G
SG
Iyengar
Sudha K
SK
Chew
Emily Y
EY
Davis
Mathew D
MD
Satko
Scott G
SG
Bowden
Donald W
DW
Duggirala
Ravi
R
Elston
Robert C
RC
Guo
Xiuxing
X
Hanson
Robert L
RL
Igo
Robert P
RP
Ipp
Eli
E
Kimmel
Paul L
PL
Knowler
William C
WC
Molineros
Julio
J
Nelson
Robert G
RG
Pahl
Madeleine V
MV
Quade
Shannon R E
SR
Rasooly
Rebekah S
RS
Rotter
Jerome I
JI
Saad
Mohammed F
MF
Scavini
Marina
M
Schelling
Jeffrey R
JR
Sedor
John R
JR
Shah
Vallabh O
VO
Zager
Philip G
PG
Abboud
Hanna E
HE