TY - JOUR
T1 - Type 2 diabetes
T2 - Evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs
AU - Ghosh, Soumitra
AU - Watanabe, Richard M.
AU - Hauser, Elizabeth R.
AU - Valle, Timo
AU - Magnuson, Victoria L.
AU - Erdos, Michael R.
AU - Langefeld, Carl D.
AU - Balow, James
AU - Ally, Delphine S.
AU - Kohtamaki, Kimmo
AU - Chines, Peter
AU - Birznieks, Gunther
AU - Kaleta, Hong Shi
AU - Musick, Anjene
AU - Te, Catherine
AU - Tannenbaum, Joyce
AU - Eldridge, William
AU - Shapiro, Shane
AU - Martin, Colin
AU - Witt, Alyson
AU - So, Alistair
AU - Chang, Jennie
AU - Shurtleff, Ben
AU - Porter, Rachel
AU - Kudelko, Kristina
AU - Unni, Arun
AU - Segal, Leonid
AU - Sharaf, Ravi
AU - Blaschak-Harvan, Jillian
AU - Eriksson, Johan
AU - Tenkula, Tuula
AU - Vidgren, Gabriele
AU - Ehnholm, Christian
AU - Tuomilehto-Wolf, Eva
AU - Hagopian, William
AU - Buchanan, Thomas A.
AU - Toomilehto, Jaakko
AU - Bergman, Richard N.
AU - Collins, Francis S.
AU - Boehnke, Michael
PY - 1999/3/2
Y1 - 1999/3/2
N2 - 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 from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, x = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q (x = 57 cM, recurrence risk, λ(s) = 1.25, P = 0.009). Weighted logarithm of odds scores of 2.00 (x = 69.5 cM, P = 0.010) and 1.92 (x = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes-related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour 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 least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity-onset diabetes of the young 1, hepatic nuclear factor 4-a (HNF-4α) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20%. We found no evidence that sequence changes in this gene accounted for the linkage results we observed.
AB - 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 from 477 Finnish families. To date, our best evidence for linkage is on chromosome 20 with potentially separable peaks located on both the long and short arms. The unweighted multipoint maximum logarithm of odds score (MLS) was 3.08 on 20p (location, x = 19.5 cM) under an additive model, whereas the weighted MLS was 2.06 on 20q (x = 57 cM, recurrence risk, λ(s) = 1.25, P = 0.009). Weighted logarithm of odds scores of 2.00 (x = 69.5 cM, P = 0.010) and 1.92 (x = 18.5 cM, P = 0.013) were also observed. Ordered subset analyses based on sibships with extreme mean values of diabetes-related quantitative traits yielded sets of families who contributed disproportionately to the peaks. Two-hour 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 least two diabetes-susceptibility genes on chromosome 20. We have also screened the gene for maturity-onset diabetes of the young 1, hepatic nuclear factor 4-a (HNF-4α) in 64 affected sibships with evidence for high chromosomal sharing at its location on chromosome 20%. We found no evidence that sequence changes in this gene accounted for the linkage results we observed.
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U2 - 10.1073/pnas.96.5.2198
DO - 10.1073/pnas.96.5.2198
M3 - Article
C2 - 10051618
AN - SCOPUS:13044277561
SN - 0027-8424
VL - 96
SP - 2198
EP - 2203
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 5
ER -