Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion
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- fgene-07-00155
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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.
Originalsprog | Engelsk |
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Artikelnummer | 155 |
Tidsskrift | Frontiers in Genetics |
Vol/bind | 7 |
Sider (fra-til) | 1-10 |
Antal sider | 10 |
ISSN | 1664-8021 |
DOI | |
Status | Udgivet - aug. 2016 |
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