title: 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.
authors.affiliation: Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. robins@hsph.harvard.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Robins
authors.forename: J W
authors.initials: JW
authors.lastname: Smoller
authors.forename: K L
authors.initials: KL
authors.lastname: Lunetta
mesh_terms: D015982:Bias; D016022:Case-Control Studies; D015984:Causality; D002874:Chromosome Mapping / Q000379:methods* / Q000592:standards*; D015897:Comorbidity; D003627:Data Interpretation, Statistical; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008957:Models, Genetic; D010641:Phenotype; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric