Testing association and maternally mediated genetic effects with the principal component analysis in case-parents...

Major advances in genotyping technology have generated high-density maps of single nucleotide polymorphism (SNP) markers that provide an unprecedented opportunity to identify genes underlying complex traits. Several family-based statistical methods showing robust population stratification have been developed to test the association between multiple markers and disease-susceptibility genes. Only a few methods focus on testing for maternally mediated genetic effects, which is a critical risk for birth defects. The present study focuses on testing for association and maternally mediated genetic effects with family-based methods.

In the present study, we proposed a new method, max_PC integrating principal component analysis, to test association or maternally mediated genetic effects with case-parent data. The proposed method only uses the genotypes of case-parents triads and accommodates missing SNP data. Our results demonstrated that this method is powerful to test association or maternally mediated genetic effects and attractive because it provides a tool for testing the null hypothesis of no association and no maternally mediated genetic effects. Simulations with the permutation procedure as well as an application in the Crohn's disease study showed that the type I error rates of the proposed statistic were nominal with slightly higher power as compared to those of the max_Z(2) test.

We conclude that the max_PC is a good approach to test association or maternally mediated genetic effects.