Genome-wide linkage scans for type 2 diabetes mellitus in four ethnically diverse populations-significant evidence for linkage on chromosome 4q in African Americans: the Family Investigation of Nephropathy and Diabetes Research Group.
BACKGROUND
Previous studies have shown that in addition to environmental influences, type 2 diabetes mellitus (T2DM) has a strong genetic component. The goal of the current study is to identify regions of linkage for T2DM in ethnically diverse populations.


METHODS
Phenotypic and genotypic data were obtained from African American (AA; total number of individuals [N] = 1004), American Indian (AI; N = 883), European American (EA; N = 537), and Mexican American (MA; N = 1634) individuals from the Family Investigation of Nephropathy and Diabetes. Non-parametric linkage analysis, using an average of 4404 SNPs, was performed in relative pairs affected with T2DM in each ethnic group. In addition, family-based tests were performed to detect association with T2DM.


RESULTS
Statistically significant evidence for linkage was observed on chromosome 4q21.1 (LOD = 3.13; genome-wide p = 0.04) in AA. In addition, a total of 11 regions showed suggestive evidence for linkage (estimated at LOD > 1.71), with the highest LOD scores on chromosomes 12q21.31 (LOD = 2.02) and 22q12.3 (LOD = 2.38) in AA, 2p11.1 (LOD = 2.23) in AI, 6p12.3 (LOD = 2.77) in EA, and 13q21.1 (LOD = . 2.24) in MA. While no region overlapped across all ethnic groups, at least five loci showing LOD > 1.71 have been identified in previously published studies.


CONCLUSIONS
The results from this study provide evidence for the presence of genes affecting T2DM on chromosomes 4q, 12q, and 22q in AA; 6p in EA; 2p in AI; and 13q in MA. The strong evidence for linkage on chromosome 4q in AA provides important information given the paucity of diabetes genetic studies in this population.
Malhotra
Alka
A
National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.
Igo
Robert P
RP
Thameem
Farook
F
Kao
W H Linda
WH
Abboud
Hanna E
HE
Adler
Sharon G
SG
Arar
Nedal H
NH
Bowden
Donald W
DW
Duggirala
Ravindranath
R
Freedman
Barry I
BI
Goddard
Katrina A B
KA
Ipp
Eli
E
Iyengar
Sudha K
SK
Kimmel
Paul L
PL
Knowler
William C
WC
Kohn
Orly
O
Leehey
David
D
Meoni
Lucy A
LA
Nelson
Robert G
RG
Nicholas
Susanne B
SB
Parekh
Rulan S
RS
Rich
Stephen S
SS
Chen
Yii-Der I
YD
Saad
Mohammed F
MF
Scavini
Marina
M
Schelling
Jeffrey R
JR
Sedor
John R
JR
Shah
Vallabh O
VO
Taylor
Kent D
KD
Thornley-Brown
Denyse
D
Zager
Philip G
PG
Horvath
Amanda
A
Hanson
Robert L
RL
D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D005190:Family; D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044382:Population Groups / Q000235:genetics; D013223:Statistics as Topic