The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability

Hsieh, H. J., Palmer, C. G. S., Harney, S., Newton, J. L., Wordsworth, P., Brown, Matthew A., & Sinsheimer, J. S. (2006) The v-MFG test: Investigating maternal, offspring and maternal-fetal genetic incompatibility effects on disease and viability. Genetic Epidemiology, 30(4), pp. 333-347.

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The MFG test is a family-based association test that detects genetic effects contributing to disease in offspring, including offspring allelic effects, maternal allelic effects and MFG incompatibility effects. Like many other family-based association tests, it assumes that the offspring survival and the offspring-parent genotypes are conditionally independent provided the offspring is affected. However, when the putative disease-increasing locus can affect another competing phenotype, for example, offspring viability, the conditional independence assumption fails and these tests could lead to incorrect conclusions regarding the role of the gene in disease. We propose the v-MFG test to adjust for the genetic effects on one phenotype, e.g., viability, when testing the effects of that locus on another phenotype, e.g., disease. Using genotype data from nuclear families containing parents and at least one affected offspring, the v-MFG test models the distribution of family genotypes conditional on offspring phenotypes. It simultaneously estimates genetic effects on two phenotypes, viability and disease. Simulations show that the v-MFG test produces accurate genetic effect estimates on disease as well as on viability under several different scenarios. It generates accurate type-I error rates and provides adequate power with moderate sample sizes to detect genetic effects on disease risk when viability is reduced. We demonstrate the v-MFG test with HLA-DRB1 data from study participants with rheumatoid arthritis (RA) and their parents, we show that the v-MFG test successfully detects an MFG incompatibility effect on RA while simultaneously adjusting for a possible viability loss.

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ID Code: 89480
Item Type: Journal Article
Refereed: Yes
Keywords: Family-based association, Gene by environment, Gene by gene, Interaction, Viability loss, HLA DR antigen, genetic association, genetic incompatibility, genetic procedures, genotype, heredity, human, major clinical study, maternal fetal genotype test, review, rheumatoid arthritis, Alleles, Arthritis, Rheumatoid, Family Health, Female, Genetic Predisposition to Disease, Genetic Screening, Histocompatibility Testing, HLA-DR Antigens, Humans, Male, Models, Genetic, Models, Statistical, Mothers, Pedigree
DOI: 10.1002/gepi.20148
ISSN: 0741-0395
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2006 Wiley-Liss, Inc.
Deposited On: 25 Oct 2015 23:45
Last Modified: 09 Jun 2016 02:47

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