A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14.
The aim of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genes that predispose to type 2 diabetes or are responsible for variability in diabetes-related traits via a positional cloning and positional candidate gene approach. In a previously published genome-wide scan of 478 Finnish affected sibling pair (ASP) families (FUSION 1), the strongest linkage results were on chromosomes 20 and 11. We now report a second genome-wide scan using an independent set of 242 Finnish ASP families (FUSION 2), a detailed analysis of the combined set of 737 FUSION 1 + 2 families (495 updated FUSION 1 families), and fine mapping of the regions of chromosomes 11 and 20. The strongest FUSION 2 linkage results were on chromosomes 6 (maximum logarithm of odds score [MLS] = 2.30 at 95 cM) and 14 (MLS = 1.80 at 57 cM). For the combined FUSION 1 + 2 families, three results were particularly notable: chromosome 11 (MLS = 2.98 at 82 cM), chromosome 14 (MLS = 2.74 at 58 cM), and chromosome 6 (MLS = 2.66 at 96 cM). We obtained smaller FUSION 1 + 2 MLSs on chromosomes X (MLS = 1.27 at 152 cM) and 20p (MLS = 1.21 at 20 cM). Among the 10 regions that showed nominally significant evidence for linkage in FUSION 1, four (on chromosomes 6, 11, 14, and X) also showed evidence for linkage in FUSION 2 and stronger evidence for linkage in the combined FUSION 1 + 2 sample.
Silander, K; Scott, LJ; Valle, TT; Mohlke, KL; Stringham, HM; Wiles, KR; Duren, WL; Doheny, KF; Pugh, EW; Chines, P; Narisu, N; White, PP; Fingerlin, TE; Jackson, AU; Li, C; Ghosh, S; Magnuson, VL; Colby, K; Erdos, MR; Hill, JE; Hollstein, P; Humphreys, KM; Kasad, RA; Lambert, J; Lazaridis, KN; Lin, G; Morales-Mena, A; Patzkowski, K; Pfahl, C; Porter, R; Rha, D; Segal, L; Suh, YD; Tovar, J; Unni, A; Welch, C; Douglas, JA; Epstein, MP; Hauser, ER; Hagopian, W; Buchanan, TA; Watanabe, RM; Bergman, RN; Tuomilehto, J; Collins, FS; Boehnke, M
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