title: Tag SNP screening of the PDCD1 gene for association with Graves' disease.
abstract: OBJECTIVE
  The Programmed Cell Death 1 gene (PDCD1) on chromosome 2q37.3 encodes PD-1 which is involved in providing a negative signal to activated T cells. Large case-control studies have shown association of PDCD1 with several autoimmune diseases although, to date, no such studies have been performed for Graves' disease (GD). The objective of our study was to investigate eight tag SNPs representing the majority of common variation in PDCD1 within a well-characterized large UK Caucasian GD dataset.
  
  
  METHODS
  A case control association study of eight polymorphisms.
  
  
  METHODS
  2671 Graves' disease patients and 864 controls.
  
  
  METHODS
  Tests for association with disease.
  
  
  RESULTS
  No association with disease was seen for any of the +4163, +5049, +5318, +5640, +5678 and +7078 SNPs genotyped in this study. Association was detected between the +2375 SNP (P = 0.021, OR = 1.14 [95% CI = 1.01-1.29]) and GD and a small protective effect was seen with the +6799 SNP genotypes (P = 0.028, OR = 0.77 [95% CI = 0.58-1.03]).
  
  
  CONCLUSIONS
  This study has, for the first time, shown that small effects within PDCD1 may contribute towards the development of GD, supporting the hypothesis that much of the currently unknown genetic contribution to GD could be due to several small genetic effects with ORs 1.2. Replication of this result is now needed to confirm our findings and justify more detailed fine mapping of a primary aetiological variant in this gene region.
authors.affiliation: Department of Medicine, Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Edgbaston, Birmingham, UK.
authors.forename: P R
authors.initials: PR
authors.lastname: Newby
authors.forename: E L
authors.initials: EL
authors.lastname: Roberts-Davies
authors.forename: O J
authors.initials: OJ
authors.lastname: Brand
authors.forename: J M
authors.initials: JM
authors.lastname: Heward
authors.forename: J A
authors.initials: JA
authors.lastname: Franklyn
authors.forename: S C L
authors.initials: SC
authors.lastname: Gough
authors.forename: M J
authors.initials: MJ
authors.lastname: Simmonds
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D030541:Databases, Genetic; D005787:Gene Frequency; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D061026:Programmed Cell Death 1 Receptor; D012306:Risk
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor