Modeling maternal-offspring gene-gene interactions: the extended-MFG test

Maternal‐fetal genotype (MFG) incompatibility is an interaction between the genes of a mother and offspring at a particular locus that adversely affects the developing fetus, thereby increasing susceptibility to disease. Statistical methods for examining MFG incompatibility as a disease risk factor...

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Bibliographic Details
Published in:Genetic epidemiology 2010-07, Vol.34 (5), p.512-521
Main Authors: Childs, Erica J., Palmer, Christina G.S., Lange, Kenneth, Sinsheimer, Janet S.
Format: Article
Language:English
Subjects:
Alleles
Computer Simulation
family based association
Family Health
Female
gene by environment
Genetic Predisposition to Disease
Genetic Testing
Genotype
Humans
Likelihood Functions
maternal-fetal interaction
Models, Genetic
Models, Statistical
Mothers
Nuclear Family
Pedigree
pedigree likelihood
Pregnancy
Risk Factors
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Summary:Maternal‐fetal genotype (MFG) incompatibility is an interaction between the genes of a mother and offspring at a particular locus that adversely affects the developing fetus, thereby increasing susceptibility to disease. Statistical methods for examining MFG incompatibility as a disease risk factor have been developed for nuclear families. Because families collected as part of a study can be large and complex, containing multiple generations and marriage loops, we create the Extended‐MFG (EMFG) Test, a model‐based likelihood approach, to allow for arbitrary family structures. We modify the MFG test by replacing the nuclear‐family based “mating type” approach with Ott's representation of a pedigree likelihood and calculating MFG incompatibility along with the Mendelian transmission probability. In order to allow for extension to arbitrary family structures, we make a slightly more stringent assumption of random mating with respect to the locus of interest. Simulations show that the EMFG test has appropriate type‐I error rate, power, and precise parameter estimation when random mating holds. Our simulations and real data example illustrate that the chief advantages of the EMFG test over the earlier nuclear family version of the MFG test are improved accuracy of parameter estimation and power gains in the presence of missing genotypes. Genet. Epidemiol. 34: 512–521, 2010.© 2010 Wiley‐Liss, Inc.
ISSN:0741-0395
1098-2272
1098-2272
DOI:10.1002/gepi.20508