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

Soumitra Ghosh, Richard M. Watanabe, Elizabeth R. Hauser, Timo Valle, Victoria L. Magnuson, Michael R. Erdos, Carl D. Langefeld, James Balow, Delphine S. Ally, Kimmo Kohtamaki, Peter Chines, Gunther Birznieks, Hong Shi Kaleta, Anjene Musick, Catherine Te, Joyce Tannenbaum, William Eldridge, Shane Shapiro, Colin Martin, Alyson WittAlistair So, Jennie Chang, Ben Shurtleff, Rachel Porter, Kristina Kudelko, Arun Unni, Leonid Segal, Ravi Sharaf, Jillian Blaschak-Harvan, Johan Eriksson, Tuula Tenkula, Gabriele Vidgren, Christian Ehnholm, Eva Tuomilehto-Wolf, William Hagopian, Thomas A. Buchanan, Jaakko Toomilehto, Richard N. Bergman, Francis S. Collins, Michael Boehnke

Research output: Contribution to journalArticlepeer-review

196 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2198-2203
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number5
DOIs
StatePublished - Mar 2 1999

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Type 2 diabetes: Evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs'. Together they form a unique fingerprint.

Cite this