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

• DOI: 10.1073/pnas.96.5.2198
• Publication Date: 2002-07-26T14:39:15Z
• Authors: 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 Witt; Alistair So; Jennie Chang; Ben Shurtleff; Rachel Porter; Kristina Kudelko; Arun Unni; Leonid Segal; Ravi Sharaf; Jillian Blaschak-...; Johan Eriksson; Tuula Tenkula; Gabriele Vidgren; Christian Ehnholm; Eva Tuomilehto-Wolf; William Hagopian; Thomas A. Buchanan; Jaakko Tuomilehto; Richard N. Bergman; Francis S. Collins; Michael Boehnke
• Keywords: Centimorgan; Linkage (software); Genetic linkage

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 linkage is on chromosome 20 with potentially separable peaks located both the long and short arms. The unweighted multipoint maximum logarithm odds score (MLS) was 3.08 20p (location, x̂ = 19.5 cM) under additive model, whereas weighted MLS 2.06 20q ( 57 cM, recurrence risk, λ̂ s 1.25, P 0.009). Weighted scores 2.00 69.5 0.010) 1.92 18.5 0.013) were also observed. Ordered subset analyses based sibships extreme mean values diabetes-related quantitative traits yielded sets families who contributed disproportionately to peaks. Two-hour glucose levels offspring diabetic individuals gave 2.12 0.0018) 9.5 cM. Evidence this other studies suggests least two diabetes-susceptibility 20. have screened gene maturity-onset young 1, hepatic nuclear factor 4-a HNF-4 α) 64 high chromosomal sharing its location 20q. found no that sequence changes accounted results we