title: Association of CD247 (CD3ζ) gene polymorphisms with T1D and AITD in the population of northern Sweden.
abstract: BACKGROUND
  T1D and AITD are autoimmune disorders commonly occurring in the same family and even in the same individual. The genetic contribution to these disorders is complex making uncovering of susceptibility genes very challenging. The general aim of this study was to identify loci and genes contributing to T1D/AITD susceptibility. Our strategy was to perform linkage and association studies in the relatively genetically homogenous population of northern Sweden. We performed a GWLS to find genomic regions linked to T1D/AITD in families from northern Sweden and we performed an association study in the families to test for association between T1D/AITD and variants in previously published candidate genes as well as a novel candidate gene, CD247.
  
  
  METHODS
  DNA prepared from 459 individuals was used to perform a linkage and an association study. The ABI PRISM Linkage Mapping Set v2.5MD10 was employed for an initial 10-cM GWLS, and additional markers were added for fine mapping. Merlin was used for linkage calculations. For the association analysis, a GoldenGate Custom Panel from Illumina containing 79 SNPs of interest was used and FBAT was used for association calculations.
  
  
  RESULTS
  Our study revealed linkage to two previously identified chromosomal regions, 4q25 and 6p22, as well as to a novel chromosomal region, 1q23. The association study replicated association to PTPN22, HLA-DRB1, INS, IFIH1, CTLA4 and C12orf30. Evidence in favor of association was also found for SNPs in the novel susceptibility gene CD247.
  
  
  CONCLUSIONS
  Several risk loci for T1D/AITD identified in published association studies were replicated in a family material, of modest size, from northern Sweden. This provides evidence that these loci confer disease susceptibility in this population and emphasizes that small to intermediate sized family studies in this population can be used in a cost-effective manner for the search of genes involved in complex diseases. The linkage study revealed a chromosomal region in which a novel T1D/AITD susceptibility gene, CD247, is located. The association study showed association between T1D/AITD and several variants in this gene. These results suggests that common susceptibility genes act in concert with variants of CD247 to generate genetic risk for T1D/AITD in this population.
authors.affiliation: Department of Medical Biosciences - Medical Genetics, Umeå University, SE-901 85, Umeå, Sweden.|EMV, Immunology, BMC, Lund University, SE-221 00, Lund, Sweden.
authors.forename: Dan
authors.initials: D
authors.lastname: Holmberg
authors.affiliation: Department of Medicine, Sunderby Hospital, SE-971 80, Luleå, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Ruikka
authors.affiliation: Department of Medical Biosciences - Medical Genetics, Umeå University, SE-901 85, Umeå, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Lindgren
authors.affiliation: Department of Medicine, Sunderby Hospital, SE-971 80, Luleå, Sweden.|Department of Public Health and Clinical Medicine, Umeå University, SE-901 85, Umeå, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Eliasson
authors.affiliation: Department of Medical Biosciences - Medical Genetics, Umeå University, SE-901 85, Umeå, Sweden. sofia.mayans@umu.se.|Department of Clinical Microbiology, Division of Immunology, Umeå University, Building 6C, SE-90185, Umeå, Sweden. sofia.mayans@umu.se.
authors.forename: Sofia
authors.initials: S
authors.lastname: Mayans
mesh_terms: D017252:CD3 Complex / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D056726:Genetic Association Studies; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013548:Sweden; D013967:Thyroiditis, Autoimmune / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D017252:CD3 Complex; C121704:CD3 antigen, zeta chain
keywords: Association; Autoimmune thyroid disease; Family; Linkage; Type 1 diabetes