Remapping the type I diabetes association of the CTLA4 locus

The Type I Diabetes Genetics Consortium genotyped 24 single-nucleotide polymorphisms (SNPs) in the CTLA4 locus in 2298 type I diabetes (T1D) nuclear families (11 159 individuals, 5003 affected) to evaluate the recognized T1D association. The 24 CTLA4 SNPs span approximately 43 kb from the 5' flanking to 3' flanking region of the gene in the middle of an extended region of linkage disequilibrium of more than 100 kb. The genotyping was performed using two technologies (Illumina GoldenGate and Sequenom iPlex) on the same samples. The genotype calls by both the methods were highly consistent (the majority >99%). Previously reported T1D association from both the +49G>A and the CT60 SNPs was replicated. The reported association of the -319C>T SNP was not replicated. Although associated with T1D risk, it is likely that neither SNP is causative, as the peak of T1D association was from the SNP rs231727 at 3' flanking of the CTLA4 gene. Comprehensive resequencing and fine mapping of the CTLA4 region are still needed to clarify the causal variants.