Genome-Wide Scan for Linkage to Type 1 Diabetes in 2,496 Multiplex Families From the Type 1 Diabetes Genetics Consortium

C. Concannon, W-M. Chen, C. Julier, Grant Morahan, B. Akolkar, H.A. Erlich, J.E. Hilner, J. Nerup, C. Nierras, F. Pocoit, J.A. Todd, S.S. Rich

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Abstract

OBJECTIVE Type 1 diabetes arises from the actions of multiple genetic and environmental risk factors. Considerable success at identifying common genetic variants that contribute to type 1 diabetes risk has come from genetic association (primarily case-control) studies. However, such studies have limited power to detect genes containing multiple rare variants that contribute significantly to disease risk.RESEARCH DESIGN AND METHODS The Type 1 Diabetes Genetics Consortium (T1DGC) has assembled a collection of 2,496 multiplex type 1 diabetic families from nine geographical regions containing 2,658 affected sib-pairs (ASPs). We describe the results of a genome-wide scan for linkage to type 1 diabetes in the T1DGC family collection.RESULTS Significant evidence of linkage to type 1 diabetes was confirmed at the HLA region on chromosome 6p21.3 (logarithm of odds [LOD] = 213.2). There was further evidence of linkage to type 1 diabetes on 6q that could not be accounted for by the major linkage signal at the HLA class II loci on chromosome 6p21. Suggestive evidence of linkage (LOD ≥2.2) was observed near CTLA4 on chromosome 2q32.3 (LOD = 3.28) and near INS (LOD = 3.16) on chromosome 11p15.5. Some evidence for linkage was also detected at two regions on chromosome 19 (LOD = 2.84 and 2.54).CONCLUSIONS Five non–HLA chromosome regions showed some evidence of linkage to type 1 diabetes. A number of previously proposed type 1 diabetes susceptibility loci, based on smaller ASP numbers, showed limited or no evidence of linkage to disease. Low-frequency susceptibility variants or clusters of loci with common alleles could contribute to the linkage signals observed.
Original languageEnglish
Pages (from-to)1018-1022
Number of pages5
JournalDiabetes
Volume58
Issue number4
Early online date9 Jan 2009
DOIs
Publication statusPublished - 1 Apr 2009

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