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

Comorbidity, the association of two disorders, occurs commonly with complex diseases. In this paper. we investigate the effects of both true (within-f amily) comorbidity and spurious comorbidity due to ascertainment bias on th e validity of both the parental and sibling control transmission/disequilib rium test. Specifically. we consider settings in which a candidate gene is unlinked to the target phenotype but is in linkage disequilibrium with a co morbid phenotype. We derive conditions under which the presence of true and /or spurious comorbidity will result in an artificial correlation between t he target phenotype and the candidate gene. (C) 2001 Wiley-Liss. Inc.