title: Genome-wide scan for linkage to type 1 diabetes in 2,496 multiplex families from the Type 1 Diabetes Genetics Consortium.
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.
  
  
  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 > or =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.
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia, USA. patcon@virginia.edu
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Chen
authors.forename: Cécile
authors.initials: C
authors.lastname: Julier
authors.forename: Grant
authors.initials: G
authors.lastname: Morahan
authors.forename: Beena
authors.initials: B
authors.lastname: Akolkar
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Joan E
authors.initials: JE
authors.lastname: Hilner
authors.forename: Jørn
authors.initials: J
authors.lastname: Nerup
authors.forename: Concepcion
authors.initials: C
authors.lastname: Nierras
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
mesh_terms: D002874:Chromosome Mapping; D002877:Chromosomes, Human; D002886:Chromosomes, Human, Pair 17; D041321:Chromosomes, Human, X; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015894:Genome, Human; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008126:Lod Score; D018570:Risk Assessment
chemical_list: D005819:Genetic Markers; D006680:HLA Antigens