Family-based association test method: age of onset traits and covariates

We apply different family-based association test (FBAT) statistics for age of onset traits to the Genetics Analysis Workshop 12, problem 2 data. To evaluate different FBAT statistics we used the software package FBAT, which allows one to evaluate any test statistic that can be expressed as the sum of products between an arbitrary function of an offspring's genotype with an arbitrary function of the offspring's phenotype even if there are missing parental information. For single nucleotide polymorphisms (SNPs) in gene 1, our age-of-onset FBAT test based on the exponential model is significantly more powerful than the test by Mokliatchouk et al. [Hum Hered 51:46-53, 2000], which is based on the Cox model. We suggest incorporating covariates into FBAT statistics by replacing the trait values by their regression residuals. For the age of onset trait statistics we find that deviance residuals have much more power than "plain" martingale residuals. We discuss why for SNPs in gene 1, the usual affectation status trait, which underlies the transmission disequilibrium test (TDT), has higher power than the age-of-onset trait. We find only weak evidence (p = 0.0002) that marker D06G032 is associated with the affectation status.