Follow-up of potential novel Graves' disease susceptibility loci, identified in the UK WTCCC genome-wide nonsynonymous SNP study

Research output: Contribution to journalArticle

Authors

  • OJ Pickles
  • S Mazumdar
  • OJ Brand
  • Jacqueline Carr-Smith
  • SHS Pearce
  • DM Evans
  • MJ Simmonds

Colleges, School and Institutes

Abstract

A recent association scan using a genome-wide set of nonsynonymous coding single-nucleotide polymorphisms (nsSNPs) conducted in four diseases including Graves' disease (GD), identified nine novel possible regions of association with GD. We used a case-control approach in an attempt to replicate association of these nine regions in an independent collection of 1578 British GD patients and 1946 matched Caucasian controls. Although none of these loci showed evidence of association with GD in the independent data set, when combined with the original Wellcome Trust Case-Control Consortium study group, minor differences in allele frequencies (P >= 10(-3)) remained in the combined collection of 5924 subjects for four of the nsSNPs, present within HDLBP, TEKT1, JSRP1 and UTX. An additional 29 Tag SNPs were screened within these four gene regions to determine if further associations could be detected. Similarly, minor differences only (P = 0.042-0.002) were detected in two HDLBP and two TEKT1 Tag SNPs in the combined UK GD collection. In conclusion, it is unlikely that the SNPs selected in this replication study have a significant effect on the risk of GD in the United Kingdom. Our study confirms the need for large data sets and stringent analysis criteria when searching for susceptibility loci in common diseases. European Journal of Human Genetics (2010) 18, 1021-1026; doi:10.1038/ejhg.2010.55; published online 5 May 2010

Details

Original languageEnglish
Pages (from-to)1021-1026
Number of pages6
JournalEuropean Journal of Human Genetics
Volume18
Issue number9
Publication statusPublished - 1 Sep 2010

Keywords

  • nonsynonymous SNPs, genome-wide screening, Graves' disease