Genome-wide scans for diabetic nephropathy and albuminuria in multiethnic populations: the family investigation of nephropathy and diabetes (FIND).
The Family Investigation of Nephropathy and Diabetes (FIND) was initiated to map genes underlying susceptibility to diabetic nephropathy. A total of 11 centers participated under a single collection protocol to recruit large numbers of diabetic sibling pairs concordant and discordant for diabetic nephropathy. We report the findings from the first-phase genetic analyses in 1,227 participants from 378 pedigrees of European-American, African-American, Mexican-American, and American Indian descent recruited from eight centers. Model-free linkage analyses, using a dichotomous definition for diabetic nephropathy in 397 sibling pairs, as well as the quantitative trait urinary albumin-to-creatinine ratio (ACR), were performed using the Haseman-Elston linkage test on 404 microsatellite markers. The strongest evidence of linkage to the diabetic nephropathy trait was on chromosomes 7q21.3, 10p15.3, 14q23.1, and 18q22.3. In ACR (883 diabetic sibling pairs), the strongest linkage signals were on chromosomes 2q14.1, 7q21.1, and 15q26.3. These results confirm regions of linkage to diabetic nephropathy on chromosomes 7q, 10p, and 18q from prior reports, making it important that genes underlying these peaks be evaluated for their contribution to nephropathy susceptibility. Large family collections consisting of multiple members with diabetes and advanced nephropathy are likely to accelerate the identification of genes causing diabetic nephropathy, a life-threatening complication of diabetes.
Iyengar
Sudha K
SK
FIND-Genetic Analysis and Data Coordinating Center, Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106-7281, USA. ski@case.edu
Abboud
Hanna E
HE
Goddard
Katrina A B
KA
Saad
Mohammed F
MF
Adler
Sharon G
SG
Arar
Nedal H
NH
Bowden
Donald W
DW
Duggirala
Ravi
R
Elston
Robert C
RC
Hanson
Robert L
RL
Ipp
Eli
E
Kao
W H Linda
WH
Kimmel
Paul L
PL
Klag
Michael J
MJ
Knowler
William C
WC
Meoni
Lucy A
LA
Nelson
Robert G
RG
Nicholas
Susanne B
SB
Pahl
Madeleine V
MV
Parekh
Rulan S
RS
Quade
Shannon R E
SR
Rich
Stephen S
SS
Rotter
Jerome I
JI
Scavini
Marina
M
Schelling
Jeffrey R
JR
Sedor
John R
JR
Sehgal
Ashwini R
AR
Shah
Vallabh O
VO
Smith
Michael W
MW
Taylor
Kent D
KD
Winkler
Cheryl A
CA
Zager
Philip G
PG
Freedman
Barry I
BI
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000235:genetics*; D002874:Chromosome Mapping; D003404:Creatinine / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005190:Family; D005260:Female; D015894:Genome, Human; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010375:Pedigree; D010641:Phenotype; D044469:Racial Groups / Q000235:genetics*
D003404:Creatinine