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

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Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion. / Huang, Lam Opal; Infante-RIvard, Claire; Labbe, Aurélie.

In: Frontiers in Genetics, Vol. 7, 155, 08.2016, p. 1-10.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Huang, LO, Infante-RIvard, C & Labbe, A 2016, 'Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion', Frontiers in Genetics, vol. 7, 155, pp. 1-10. https://doi.org/10.3389/fgene.2016.00155

APA

Huang, L. O., Infante-RIvard, C., & Labbe, A. (2016). Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion. Frontiers in Genetics, 7, 1-10. [155]. https://doi.org/10.3389/fgene.2016.00155

Vancouver

Huang LO, Infante-RIvard C, Labbe A. Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion. Frontiers in Genetics. 2016 Aug;7:1-10. 155. https://doi.org/10.3389/fgene.2016.00155

Author

Huang, Lam Opal ; Infante-RIvard, Claire ; Labbe, Aurélie. / Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion. In: Frontiers in Genetics. 2016 ; Vol. 7. pp. 1-10.

Bibtex

@article{91fe7564e7a34e30ba508d7e00b5905b,
title = "Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion",
abstract = "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.",
keywords = "Faculty of Health and Medical Sciences",
author = "Huang, {Lam Opal} and Claire Infante-RIvard and Aur{\'e}lie Labbe",
note = "The Supplementary Material for this article can be found online at: https://www.frontiersin.org/article/10.3389/fgene.2016.00155",
year = "2016",
month = "8",
doi = "10.3389/fgene.2016.00155",
language = "English",
volume = "7",
pages = "1--10",
journal = "Frontiers in Genetics",
issn = "1664-8021",
publisher = "Frontiers Media S.A.",

}

RIS

TY - JOUR

T1 - Analysis of Case-Parent Trios Using a Loglinear Model with Adjustment for Transmission Ratio Distortion

AU - Huang, Lam Opal

AU - Infante-RIvard, Claire

AU - Labbe, Aurélie

N1 - The Supplementary Material for this article can be found online at: https://www.frontiersin.org/article/10.3389/fgene.2016.00155

PY - 2016/8

Y1 - 2016/8

N2 - 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.

AB - 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.

KW - Faculty of Health and Medical Sciences

U2 - 10.3389/fgene.2016.00155

DO - 10.3389/fgene.2016.00155

M3 - Journal article

VL - 7

SP - 1

EP - 10

JO - Frontiers in Genetics

JF - Frontiers in Genetics

SN - 1664-8021

M1 - 155

ER -

ID: 189420235