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

作者：Huang Lam O^*; Infante Rivard Claire; Labbe Aurelie

来源：Frontiers in Genetics, 2016, 7: 155.

DOI：10.3389/fgene.2016.00155

• Transmission Ratio Distortion
• meiotic drive
• family-based association analysis
• log-linear model
• case-parent triad
• case-parent trios
• intrauterine growth restriction
• intrauterine growth retardation

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.

• 出版日期2016-8-31