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-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.
Robins
J M
JM
Department of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Massachusetts 02115, USA. robins@hsph.harvard.edu
Smoller
J W
JW
Lunetta
K L
KL
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