Family-based association tests for qualitative and quantitative traits using single-nucleotide polymorphism and microsatellite data

Using the Genetic Analysis Workshop 12 simulated data, we contrasted result s for association tests in nuclear families and extended pedigrees using si ngle-nucleotide polymorphism (SNP) data, and we compared results for differ ent trait definitions, for outbred and isolate populations, and for SN? and microsatellite data. SNPs in major genes 1 and 6 were analyzed using trans mission disequilibrium testing (TDT) [Spielman et al., Am J Hum Genet 52:50 6-16, 1993], sibship disequilibrium testing (SDT) [Horvath and Laird, Am J Hum Genet 63:1886-97, 1998], family-based association testing (FBAT) [Horva th et al., Eur J Hum Genet 9:301-6, 2001], and a chi-square analysis of fou nders. TDT and SDT were applied in a sample of independent nuclear families , while FBAT was applied in extended pedigrees. SNPs and microsatellites we re analyzed with dichotomous and quantitative trait definitions using FBAT in the isolate and outbred populations. The results of the TDT, SDT, and FB AT analyses are comparable using SNP data to identify the disease gene. How ever, these tests of association were not helpful in discriminating between functional and nonfunctional SNPs in disequilibrium. SNP data were able to identify association with affection status in a gene that influences the l iability directly (MG6), but did not perform as well when assessing associa tion with affection status in a gene that influences the outcome only throu gh a quantitative trait (MG1). Association with MG1 was observed using the SNP data when the outcome was defined quantitatively. Microsatellite data w ere relatively unsuccessful in identifying association with the markers in the region of a major gene. The magnitude of the associations between SNPs and the dichotomous or quantitative trait definitions were similar in the o utbred and isolated populations. ((C)) 2001 Wiley-Liss, Inc.