The Finland-United States investigation of non-insulin-dependent diabetes mellitus genetics (FUSION) study. I. An autosomal genome scan for genes that predispose to type 2 diabetes.
We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P=.0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P=.00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes.
Ghosh
S
S
Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, MD, USA.
Watanabe
R M
RM
Valle
T T
TT
Hauser
E R
ER
Magnuson
V L
VL
Langefeld
C D
CD
Ally
D S
DS
Mohlke
K L
KL
Silander
K
K
Kohtamäki
K
K
Chines
P
P
Balow
J
J
Birznieks
G
G
Chang
J
J
Eldridge
W
W
Erdos
M R
MR
Karanjawala
Z E
ZE
Knapp
J I
JI
Kudelko
K
K
Martin
C
C
Morales-Mena
A
A
Musick
A
A
Musick
T
T
Pfahl
C
C
Porter
R
R
Rayman
J B
JB
D000368:Aged; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D005215:Fasting; D005260:Female; D005387:Finland; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008126:Lod Score; D008297:Male; D016555:Matched-Pair Analysis; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D009679:Nuclear Family; D019655:Quantitative Trait, Heritable; D014481:United States