Genome-wide scan for estimated glomerular filtration rate in multi-ethnic diabetic populations: the Family Investigation of Nephropathy and Diabetes (FIND).
OBJECTIVE
Diabetic nephropathy, the most common cause of end-stage renal disease, aggregates in families and specific ethnic groups. Deconstructing diabetic nephropathy into intermediate, quantitative phenotypes may increase feasibility of detecting susceptibility loci by genetic screens. Glomerular filtration rate (GFR), which characterizes diabetic nephropathy, was employed as a quantitative trait in a preliminary whole-genome scan.


METHODS
Estimated GFR (eGFR) was calculated for 882 diabetic sibpairs (mean age 57 years) of African-American (25.6% of total), American Indian (8.6%), European-American (14.2%), and Mexican-American (51.6%) descent enrolled in the initial phase of the Family Investigation of Nephropathy and Diabetes (FIND). A whole-genome scan was performed using 404 microsatellite markers (average spacing 9 cM) and model-free linkage analysis.


RESULTS
For all ethnicities combined, strong evidence for linkage was observed on chromosomes 1q43 (P = 3.6 x 10(-3)), 7q36.1 (P = 2.1 x 10(-4)), 8q13.3 (P = 4.6 x 10(-4)), and 18q23.3 (P = 2.7 x 10(-3)). Mexican-American families, who comprised the major ethnic subpopulation in FIND, contributed to linkage on chromosomes 1q43, 2p13.3, 7q36.1, 8q13.3, and 18q23.3, whereas African-American and American-Indian families displayed linkage peaks on chromosomes 11p15.1 and 15q22.3, respectively.


CONCLUSIONS
We have demonstrated multiple chromosomal regions linked to eGFR in a multi-ethnic collection of families ascertained by a proband with diabetic nephropathy. Identification of genetic variants within these loci that are responsible for the linkage signals could lead to predictive tests or novel therapies for subsets of patients at risk for diabetic nephropathy.
Schelling
Jeffrey R
JR
Department of Epidemiology and Biostatistics, Case Western Reserve University, Wolstein Research Building, Rm. 1300, 10900 Euclid Ave., Cleveland, OH 44106-7281, USA.
Abboud
Hanna E
HE
Nicholas
Susanne B
SB
Pahl
Madeleine V
MV
Sedor
John R
JR
Adler
Sharon G
SG
Arar
Nedal H
NH
Bowden
Donald W
DW
Elston
Robert C
RC
Freedman
Barry I
BI
Goddard
Katrina A B
KA
Guo
Xiuqing
X
Hanson
Robert L
RL
Ipp
Eli
E
Iyengar
Sudha K
SK
Jun
Gyungah
G
Kao
W H Linda
WH
Kasinath
Balakuntalam S
BS
Kimmel
Paul L
PL
Klag
Michael J
MJ
Knowler
William C
WC
Nelson
Robert G
RG
Parekh
Rulan S
RS
Quade
Shannon R
SR
Rich
Stephen S
SS
Saad
Mohammed F
MF
Scavini
Marina
M
Smith
Michael W
MW
Taylor
Kent
K
Winkler
Cheryl A
CA
Zager
Philip G
PG
Shah
Vallabh O
VO
D044383:Black People / Q000235:genetics; D003920:Diabetes Mellitus / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005006:Ethnicity; D005260:Female; D008040:Genetic Linkage; D015894:Genome, Human; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D035781:Siblings; D044465:White People / Q000235:genetics; D001741:Black or African American