Using single nucleotide, polymorphisms to investigate association between a candidate gene and disease

A range of study designs, using unrelated or family controls, were used to investigate the pattern of association with disease of single nucleotide po lymorphisms (SNPs) within candidate gene I (simulated data). Strong evidenc e of disease association at the functional locus was detected using all stu dy designs, and in the "general" but not the "isolated" population the func tional polymorphism displayed considerably higher association than surround ing SNPs. There was much variation in the strength of association of SNPs w ith disease, up to 70% of which was explained by SNP allele frequency and d istance from the functional polymorphism. Some common polymorphisms very cl ose to the functional locus however showed no association with disease. Ana lysis of short haplotypes of SNPs reduced but did not totally remove this f eature. (C) 2001 Wiley-Liss, Inc.