The problems of using the transmission/disequilibrium test to infer tight linkage

Family-based association methods such as the transmission/disequilibrium te st (TDT) have become very popular during the past few years, often being pr eferred to case-control studies because family-based approaches avoid the d ifficulties of ascertainment of appropriate populations of cases and contro ls for case-control studies. Significant TDT results indicate both linkage and allelic association. However, significant TDT results are often interpr eted as implying tight linkage of marker and disease locus, and we shall ar gue here that, in general, this interpretation is not justified.