Examination of candidate chromosomal regions for type 2 diabetes reveals a susceptibility locus on human chromosome 8p23.1.
In a panel of large Caucasian pedigrees, we genotyped markers in eight chromosomal regions previously reported as supporting linkage with type 2 diabetes. We previously reported significant linkage on chromosome 20q (maximum logarithm of odds score [MLS] = 2.79) in this panel. In the present analysis, candidate regions on 1q, 2q, 3q, 5q, 9q, and 10q yielded little evidence for linkage; a region on 2p (MLS = 1.64, P = 0.01 at position 9.0 cM) gave suggestive evidence of linkage; and a region on 8p (MLS = 3.67, P = 2.8 x 10(-5), at position 7.6 cM) gave significant evidence of linkage. Conditional analyses were performed for both 2p and 8p regions and the region reported on 20q. The MLS for 2p increased from 1.64 to 1.79 (empirical P = 0.142) when conditioned for heterogeneity on 20q. The case was similar for 8p, where the MLS increased from 3.67 to 4.51 (empirical P = 0.023) when conditioned on families without evidence of linkage at 20q. In conclusion, our data support a type 2 diabetes susceptibility locus on chromosome 8p that appears to be independent from other susceptibility loci. Although we were able to replicate linkage in our pedigrees on chromosome 2p, we did not find evidence of linkage for regions on 1q, 2q, 3q, 5q, 9q, or 10q.
Pezzolesi
Marcus G
MG
Section on Genetics and Epidemiology, Joslin Diabetes Center, Boston, Massachusetts, USA.
Nam
Moonsuk
M
Nagase
Terumasa
T
Klupa
Tomasz
T
Dunn
Jonathon S
JS
Mlynarski
Wojciech M
WM
Rich
Stephen S
SS
Warram
James H
JH
Krolewski
Andrzej S
AS
D017668:Age of Onset; D001835:Body Weight; D002874:Chromosome Mapping / Q000379:methods; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio