A Large Set of Finnish Affected Sibling Pair Families With Type 2 Diabetes Suggests Susceptibility Loci on Chromosomes 6, 11, and 14
Author:
Silander Kaisa1, Scott Laura J.2, Valle Timo T.3, Mohlke Karen L.1, Stringham Heather M.2, Wiles Kerry R.1, Duren William L.2, Doheny Kimberly F.4, Pugh Elizabeth W.4, Chines Peter1, Narisu Narisu1, White Peggy P.2, Fingerlin Tasha E.2, Jackson Anne U.2, Li Chun2, Ghosh Soumitra1, Magnuson Victoria L.1, Colby Kimberly1, Erdos Michael R.1, Hill Jason E.1, Hollstein Pablo1, Humphreys Kathleen M.1, Kasad Roshni A.1, Lambert Jessica1, Lazaridis Konstantinos N.1, Lin George1, Morales-Mena Anabelle1, Patzkowski Kristin1, Pfahl Carrie1, Porter Rachel1, Rha David1, Segal Leonid1, Suh Yong D.1, Tovar Jason1, Unni Arun1, Welch Christian1, Douglas Julie A.2, Epstein Michael P.2, Hauser Elizabeth R.2, Hagopian William5, Buchanan Thomas A.6, Watanabe Richard M.27, Bergman Richard N.8, Tuomilehto Jaakko39, Collins Francis S.1, Boehnke Michael2
Affiliation:
1. Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland 2. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan 3. Diabetes and Genetic Epidemiology Unit, Department of Epidemiology and Health Promotion, and Department of Biochemistry, National Public Health Institute, Helsinki, Finland 4. Center for Inherited Disease Research, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 5. Pacific Northwest Research Institute, Seattle, Washington 6. Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 7. Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 8. Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 9. Department of Public Health, University of Helsinki, Helsinki, Finland
Abstract
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.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
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