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Diabetes 54:2655-2662, 2005
© 2005 by the American Diabetes Association, Inc.

Genome-Wide Linkage Analyses of Type 2 Diabetes in Mexican Americans

The San Antonio Family Diabetes/Gallbladder Study

Kelly J. Hunt1, Donna M. Lehman1, Rector Arya1, Sharon Fowler1, Robin J. Leach2, Harald H.H. Göring3, Laura Almasy3, John Blangero3, Tom D. Dyer3, Ravindranath Duggirala3, and Michael P. Stern1

1 Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center, San Antonio, Texas
2 Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas
3 Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas

The San Antonio Family Diabetes/Gallbladder Study was initiated to identify susceptibility genes for type 2 diabetes. Evidence was previously reported of linkage to diabetes on 10q with suggestive evidence on 3p and 9p in a genome-wide scan of 440 individuals from 27 pedigrees ascertained through a single diabetic proband. Subsequently, the study was expanded to include 906 individuals from 39 extended Mexican-American pedigrees, two additional examination cycles ~5.3 and 7.6 years after baseline, and genotypes for a new set of genome-wide markers. Therefore, we completed a second genome-wide linkage scan. Using information from a participant’s most recent exam, the prevalence of diabetes in nonprobands was 21.8%. We performed genome-wide variance components-based genetic analysis on the discrete trait diabetes using a liability model and on the quantitative Martingale residual obtained from modeling age of diabetes diagnosis using Cox proportional hazard models. Controlling for age and age2, our strongest evidence for linkage to the trait diabetes and the quantitative Martingale residual was on chromosome 3p at marker D3S2406 with multipoint empirical logarithm of odds scores of 1.87 and 3.76, respectively. In summary, we report evidence for linkage to diabetes on chromosome 3p in a region previously identified in at least three independent populations.

Address correspondence and reprint requests to Kelly J. Hunt, PhD, Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229-3900. E-mail: huntk{at}uthscsa.edu

Abbreviations: CIDR, Center for Inherited Disease Research; LOD, logarithm of odds; SAFDGS, San Antonio Family Diabetes/Gallbladder Study; WHO, World Health Organization


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