Analytical approaches to detect maternal/fetal genotype incompatibilities that increase risk of pre-eclampsia

dc.contributor.authorParimi, Neeta
dc.contributor.authorTromp, Gerard
dc.contributor.authorKuivaniemi, Helena
dc.contributor.authorNien, Jyh K.
dc.contributor.authorGomez, Ricardo
dc.contributor.authorRomero, Roberto
dc.contributor.authorGoddard, Katrina A.
dc.date.accessioned2019-10-17T14:33:06Z
dc.date.available2019-10-17T14:33:06Z
dc.date.issued2008
dc.date.updated2019-10-14T18:46:55Z
dc.description.abstractAbstract Background In utero interactions between incompatible maternal and fetal genotypes are a potential mechanism for the onset or progression of pregnancy related diseases such as pre-eclampsia (PE). However, the optimal analytical approach and study design for evaluating incompatible maternal/offspring genotype combinations is unclear. Methods Using simulation, we estimated the type I error and power of incompatible maternal/offspring genotype models for two analytical approaches: logistic regression used with case-control mother/offspring pairs and the log-linear regression used with case-parent triads. We evaluated a real dataset consisting of maternal/offspring pairs with and without PE for incompatibility effects using the optimal analysis based on the results of the simulation study. Results We identified a single coding scheme for the incompatibility effect that was equally or more powerful than all of the alternative analysis models evaluated, regardless of the true underlying model for the incompatibility effect. In addition, the log-linear regression was more powerful than the logistic regression when the heritability was low, and more robust to adjustment for maternal or fetal effects. For the PE data, this analysis revealed three genes, lymphotoxin alpha (LTA), von Willebrand factor (VWF), and alpha 2 chain of type IV collagen (COL4A2) with possible incompatibility effects. Conclusion The incompatibility model should be evaluated for complications of pregnancy, such as PE, where the genotypes of two individuals may contribute to the presence of disease.Abstract Background In utero interactions between incompatible maternal and fetal genotypes are a potential mechanism for the onset or progression of pregnancy related diseases such as pre-eclampsia (PE). However, the optimal analytical approach and study design for evaluating incompatible maternal/offspring genotype combinations is unclear. Methods Using simulation, we estimated the type I error and power of incompatible maternal/offspring genotype models for two analytical approaches: logistic regression used with case-control mother/offspring pairs and the log-linear regression used with case-parent triads. We evaluated a real dataset consisting of maternal/offspring pairs with and without PE for incompatibility effects using the optimal analysis based on the results of the simulation study. Results We identified a single coding scheme for the incompatibility effect that was equally or more powerful than all of the alternative analysis models evaluated, regardless of the true underlying model for the incompatibility effect. In addition, the log-linear regression was more powerful than the logistic regression when the heritability was low, and more robust to adjustment for maternal or fetal effects. For the PE data, this analysis revealed three genes, lymphotoxin alpha (LTA), von Willebrand factor (VWF), and alpha 2 chain of type IV collagen (COL4A2) with possible incompatibility effects. Conclusion The incompatibility model should be evaluated for complications of pregnancy, such as PE, where the genotypes of two individuals may contribute to the presence of disease.
dc.fuente.origenBiomed Central
dc.identifier.citationBMC Medical Genetics. 2008 Jul 03;9(1):60
dc.identifier.doi10.1186/1471-2350-9-60
dc.identifier.urihttps://doi.org/10.1186/1471-2350-9-60
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/26710
dc.issue.numeroNo. 60
dc.language.isoen
dc.nota.accesoContenido completo
dc.pagina.final14
dc.pagina.inicio1
dc.revistaBMC Medical Geneticses_ES
dc.rightsacceso abierto
dc.rights.holderParimi et al; licensee BioMed Central Ltd.
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.subject.otherÚtero - Enfermedadeses_ES
dc.subject.otherEmbarazo - Diagnosticoes_ES
dc.subject.otherPreeclampsiaes_ES
dc.titleAnalytical approaches to detect maternal/fetal genotype incompatibilities that increase risk of pre-eclampsiaes_ES
dc.typeartículo
dc.volumenVol. 9
sipa.codpersvinculados80926
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
12881_2007_Article_354.pdf
Size:
536.91 KB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
0 B
Format:
Item-specific license agreed upon to submission
Description: