Type 2 diabetes: Evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs

We are conducting a genome scan at an average resolution of 10 centimorgans (cM) for type 2 diabetes susceptibility genes in 716 affected sib pairs fr om 477 Finnish families. To date, our best evidence for linkage is on chrom osome 20 with potentially separable peaks located on both the long and shor t arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, (x) over cap = 19.5 cM) under an additive model, wh ereas the weighted MLS was 2.06 on 20q ((x) over cap = 57 cM, recurrence ri sk, <(lambda)over cap>(s) = 1.25, P = 0.009). Weighted logarithm of odds sc ores of 2.00 ((x) over cap = 69.5 cM,P = 0.010) and 1.92 ((x) over cap = 18 .5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibs hips with extreme mean values of diabetes related quantitative traits yield ed sets of families who contributed disproportionately to the peaks. Two-ho ur glucose levels in offspring of diabetic individuals gave a MLS of 2.12 ( P = 0.0018) at 9.5 cM. Evidence from this and other studies suggests at lea st two diabetes-susceptibility genes on chromosome 20. We have also screene d the gene for maturity onset diabetes of the young I, hepatic nuclear fact or 4-a (HNF-4 alpha) in 64 affected sibships with evidence for high chromos omal sharing at its location on chromosome 20q. We found no evidence that s equence changes in this gene accounted for the linkage results we observed.