1. ¹Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge, UK
2. ²Department of Medical Genetics, Queen's University Belfast, Belfast City Hospital, Belfast, UK
3. ³Clinic of Diabetes, Institute of Diabetes, Nutrition and Metabolic Diseases 'N Paulescu', Bucharest, Romania
4. ⁴Diabetes and Genetic Epidemiology Unit, National Public Health Institute, University of Helsinki, Helsinki, Finland
5. ⁵Department of Public Health, University of Helsinki, Helsinki, Finland

Correspondence: DG Clayton, Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust/MRC Building, Cambridge CB2 2XY, UK. E-mail: david.clayton@cimr.cam.ac.uk

⁶These authors contributed equally to this work

Received 30 September 2003; Revised 16 January 2004; Accepted 28 January 2004; Published online 18 March 2004.

Abstract

We have previously shown that the selection of haplotype tag single nucleotide polymorphisms (htSNPs) and their statistical analysis in a multi-locus transmission/disequilibrium test (TDT) results in a more cost-effective genotyping strategy in disease association studies of genes by minimising redundancy due to linkage disequilibrium between SNPs. Further savings can be achieved by the use of a two-stage genotyping strategy. This approach is illustrated here in conjunction with the multi-locus TDT in determining whether common alleles of the immune regulatory genes RANK and its ligand TRANCE (RANKL) are associated with type 1 diabetes (T1D). A saving of approximately 75% of potential genotyping reactions could be made with minimal loss of power. There was little evidence from our analysis for association between the TRANCE and RANK genes and T1D in the populations tested.