Application of family-based association testing to assess the genotype-phenotype association involved in complex traits using single-nucleotide polymorphisms.
BACKGROUND
We used the FBAT (family-based association test) software to test for association between 300 individual single-nucleotide polymorphisms and P1 (a latent trait of Kofendred Personality Disorder) in 100 simulated replicates of the Aipotu population. Using the Genetic Analysis Workshop 14 dataset, we calculated the power of FBAT to detect linkage disequilibrium on chromosome 3 (D2). Also, we calculated the false-positive rate on chromosome 1, which contains a true locus (D1) but no linkage disequilibrium was simulated between the trait and all the surrounding single-nucleotide polymorphisms.


RESULTS
We were able to detect the associations between phenotype P1 and three adjacent markers B03T3056 (average p-value = 0.0002), B03T3057 (average p-value = 0.00072), and B03T3058 (average p-value = 0.0038) with power of 98%, 87%, 71% on chromosome 3, respectively. The overall false positive rate to detect association was 0.06 on chromosome 1.


CONCLUSIONS
The power to detect a significant association in 100 nuclear families affected with the latent trait of Kofendred Personality Disorder by using FBAT was reasonable (based on 100 replicates). In the future, we will compare the performance of FBAT with alternative approaches, such as using FBAT-generalized estimating equations methods to test for association in families affected with complex traits.
Wang
Ming-Hsi
MH
Department of Epidemiology, Bloomberg School of Public Health, 615 North Work Street, Johns Hopkins University, Baltimore, Maryland 21205, USA. mwang2@jhsph.edu
Guo
Mitchell
M
Shugart
Yin Y
YY
D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D005190:Family; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019655:Quantitative Trait, Heritable; D015203:Reproducibility of Results