The family based association test method: strategies for studying general genotype-phenotype associations

With possibly incomplete nuclear families, the family based association tes t (FBAT) method allows one to evaluate any test statistic that can be expre ssed as the sum of products (covariance) between an arbitrary function of a n offspring's genotype with an arbitrary function of the offspring's phenot ype. We derive expressions needed to calculate the mean and variance of the se test statistics under the null hypothesis of no linkage. To give some gu idance on using the FBAT method, we present three simple data analysis stra tegies for different phenotypes: dichotomous (affection status), quantitati ve and censored (eg, the age of onset). We illustrate the approach by apply ing it to candidate gene data of the NIMH Alzheimer Disease Initiative. We show that the RC-TDT is equivalent to a special case of the FBAT method. Th is result allows us to generalise the RC-TDT to dominant, recessive and mul ti-allelic marker codings. Simulations compare the resulting FBAT tests to the RC-TDT and the S-TDT. The FBAT software is freely available.