Modeling the Effects of Maternal-fetal Genotype Incompatibility on Disease Risk When Fetal Viability is Reduced

• Activity Number: 166
• Type: Contributed
• Date/Time: Monday, August 9, 2004 : 2:00 PM to 3:50 PM
• Sponsor: Section on Statistics in Epidemiology
• Author(s): Hsin-Ju Hsieh*+ and Christina Palmer and Janet Sinsheimer
• Companies: University of California, Los Angeles and University of California, Los Angeles and University of California, Los Angeles
• Keywords: log-linear model ; genetic epidemiology ; genotype interaction ; conditional likelihood ; gene-mapping ; confounders

Abstract

Genotype incompatibility between a mother and fetus can create adverse prenatal conditions that can potentially increase disease susceptibility, even into adulthood. Maternal-fetal genotype (MFG) incompatibility may also reduce fetal viability, so that potentially affected individuals are not observed. Sinsheimer et al. (2003) proposed the MFG test, a loglinear model, using case-parent trios to examine incompatibility but the effect estimated from their method cannot distinguish between a fetal viability and an incompatibility effect. We propose a new method that extends the multiple sibling version of the conditional likelihood model of Kraft et al. (in press). We model both incompatibility and fetal viability in a joint distribution of the children's and parents' genotypes conditional on the children's affection status. The model is robust and has the appropriate Type I error rate. Through simulation, we show that moderate sample sizes can provide significant power to detect MFG incompatibility effect on disease risk when fetal viability is reduced, and ignoring fetal viability in analysis may underestimate disease relative risk due to the MFG incompatibility.