On the validity of the TDT test in the presence of comorbidity and ascertainment bias

Abstract

Comorbidity, the association of two disorders, occurs commonly with complex diseases. In this paper, we investigate the effects of both true (within-family) comorbidity and spurious comorbidity due to ascertainment bias on the validity of both the parental and sibling control transmission/disequilibrium test. Specifically, we consider settings in which a candidate gene is unlinked to the target phenotype but is in linkage disequilibrium with a comorbid phenotype. We derive conditions under which the presence of true and/or spurious comorbidity will result in an artificial correlation between the target phenotype and the candidate gene.