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22 Zygosity Diagnosis in the Absence of Genotypic Data An Approach Using Latent Class Analy.pdf

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22 Zygosity Diagnosis in the Absence of Genotypic Data An Approach Using Latent Class Analy

22 Twin Research Volume 6 Number 1 pp. 22± 26 For zygosity diagnosis in the absence of genotypic data, or inthe recruitment phase of a twin study where only single twins from same-sex pairs are being screened, or to provide a test for sample duplication leading to the false identification of a dizygotic pair as monozygotic, the appropriate analysis of respondents’ answers to questions about zygosity is critical. Using data from a young adult Australian twin cohort (N = 2094 complete pairs and 519 singleton twins from same-sex pairs with complete responses to all zygosity items), we show that application of latent class analysis (LCA), fitting a 2-class model, yields results that show good concordance with tradi- t ional methods of zygosity diagnosis, but with certa in important advantages. These include the ability, in many cases, to assign zygosity with specified probability on the basis of responses of a single informant (advantageous when one zygosity type is being oversampled); and the ability to quantify the probability of misassignment of zygosity, allowing prioritiza- tion of cases for genotyping as well as identification of cases of probable laboratory error. Out of 242 twins (from 121 like- sex pairs) where genotypic data were available for zygosity confirmation, only a single case was identified of incorrect zygosity assignment by the latent class algorithm. Zygosity assignment for that single case was identified by the LCA as uncertain (probability of being a monozygotic twin only 76%), and the co-twin’s responses clearly identified the pair as dizy- gotic (probability of being dizygotic 100%). In the absence of genotypic data, or as a safeguard against sample duplication, application of LCA for zygosity assignment or confirmation is strongly recommended. Historically, early twin studies relied upon questionnaire- based assessment of twin pair zygosity, using questions about physical similarity and confusion in childhood, with typing of genetic markers