Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion

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Lam Opal Huang, Claire Infante-RIvard, Aurélie Labbe

Transmission of the two parental alleles to offspring deviating from the Mendelian ratio is termed Transmission Ratio Distortion (TRD), occurs throughout gametic and embryonic development. TRD has been well-studied in animals, but remains largely unknown in humans. The Transmission Disequilibrium Test (TDT) was first proposed to test for association and linkage in case-trios (affected offspring and parents); adjusting for TRD using control-trios was recommended. However, the TDT does not provide risk parameter estimates for different genetic models. A loglinear model was later proposed to provide child and maternal relative risk (RR) estimates of disease, assuming Mendelian transmission. Results from our simulation study showed that case-trios RR estimates using this model are biased in the presence of TRD; power and Type 1 error are compromised. We propose an extended loglinear model adjusting for TRD. Under this extended model, RR estimates, power and Type 1 error are correctly restored. We applied this model to an intrauterine growth restriction dataset, and showed consistent results with a previous approach that adjusted for TRD using control-trios. Our findings suggested the need to adjust for TRD in avoiding spurious results. Documenting TRD in the population is therefore essential for the correct interpretation of genetic association studies.
Original languageEnglish
Article number155
JournalFrontiers in Genetics
Volume7
Pages (from-to)1-10
Number of pages10
ISSN1664-8021
DOIs
Publication statusPublished - Aug 2016

Bibliographical note

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/article/10.3389/fgene.2016.00155

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