A range of study designs, using unrelated or family controls, were used to investigate the pattern of association with disease of single nucleotide polymorphisms (SNPs) within candidate gene 1 (simulated data). Strong evidence of disease association at the functional locus was detected using all study designs, and in the "general" but not the "isolated" population the functional polymorphism displayed considerably higher association than surrounding SNPs. There was much variation in the strength of association of SNPs with disease, up to 70% of which was explained by SNP allele frequency and distance from the functional polymorphism. Some common polymorphisms very close to the functional locus however showed no association with disease. Analysis of short haplotypes of SNPs reduced but did not totally remove this feature.