The estimation of probandwise concordance in twins: the effect of unequal ascertainment.
This report examines the impact of two major kinds of unequal ascertainment on the estimation of true probandwise concordance (Cpbt) in twin studies: 1) concordance-dependent - where the ascertainment rate differs in affected members of concordant vs discordant pairs, and 2) non-independent - where ascertainment rates differ in affected members of concordant pairs where the cotwin has vs has not been ascertained. Concordance-dependent ascertainment is easily modeled algebraically; non-independent ascertainment is more complex and we here propose a model based on survival analysis. Overall, concordance-dependent ascertainment produces greater bias in estimates of probandwise concordance than does non-independent ascertainment. The bias introduced by concordance-dependent ascertainment is greatest when Cpbt is low and/or when the ascertainment rate for twins in concordant pairs is low. The bias introduced by non-independent ascertainment is greatest when Cpbt is high and/or when the ascertainment probability for an affected twin in a concordant pair where the cotwin has already been ascertained approaches unity. The impact of concordance-dependent and non-independent ascertainment on estimates of heritability and common environment is examined. Correction terms to estimate Cpbt in the presence of concordance-dependent and/or non-independent ascertainment are presented.
Kendler
K S
KS
Department of Psychiatry, Virginia Commonwealth University/Medical College, Richmond.
Eaves
L J
LJ
D015982:Bias; D004200:Diseases in Twins / Q000453:epidemiology*; D006801:Humans; D015233:Models, Statistical; D011336:Probability; D015996:Survival Rate