The Q-MFG Test: A Linear Mixed Effect Model to Detect Maternal-Offspring Genetic Effects

• Activity Number: 353
• Type: Contributed
• Date/Time: Tuesday, August 11, 2015 : 10:30 AM to 12:20 PM
• Sponsor: Section on Statistics in Genomics and Genetics
• Author(s): Michelle M. Creek* and Eric M. Sobel and Janet S. Sinsheimer
• Companies: UCLA and UCLA and UCLA
• Keywords: linear mixed models ; family based association ; score test ; gene-gene interaction ; genomics

Abstract

Joint maternal and offspring genetic effects, aka maternal-fetal genotype (MFG) incompatibilities, are often neglected in studies of complex diseases and quantitative traits. They are implicated in perinatal and adult onset diseases but there are only limited ways to investigate their influence on quantitative traits. We present the Quantitative-MFG (Q-MFG) test, a linear mixed modeling approach. Maternal and offspring genotypes are fixed and residual familial correlations are random effects. The model handles general pedigrees, common or unusual scenarios of MFG incompatibility, and additional covariates. It allows use of score tests or likelihood ratio tests (LRT). Through simulations, we evaluate test properties. The LRT leads to correct parameter estimates and the score test provides equivalent inference to the LRT. With both simulated and actual data we show that the score test is an effective and rapid screening tool for genome wide association studies.