Susceptibility scoring in family-based association testing

Background: Family-based association testing is an important part of genetic epidemiology. Tests are available to include multiple siblings, unaffected offspring, and to adjust for environmental covariates. We explore a susceptibility residual method of adjustment for covariates. Results: Through simulation, we show that environmental adjustments that down-weight persons who are destined to be affected decrease the power to detect genetic association. We used the residual adjusted method on the Framingham Heart Study offspring data, provided for Genetic Analysis Workshop 13, and got mixed results. Conclusion: When the genetic effect and environmental effects are independent, a susceptibility residual method of adjustment for environmental covariates reduces the power of the association test. Further study is necessary to determine if residual adjustment is appropriate in more complex disease models.