Abstract
Gene-environment (GE) interaction has important implications in the etiology of complex diseases that are caused by a combination of genetic factors and environment variables. Several authors have developed GE analysis in the context of independent subjects or longitudinal data using a gene-set. In this paper, we propose to analyze GE interaction for discrete and continuous phenotypes in family studies by incorporating the relatedness among the relatives for each family into a generalized linear mixed model (GLMM) and by using a gene-based variance component test. In addition, we deal with collinearity problems arising from linkage disequilibrium among single nucleotide polymorphisms (SNPs) by considering their coefficients as random effects under the null model estimation. We show that the best linear unbiased predictor (BLUP) of such random effects in the GLMM is equivalent to the ridge regression estimator. This equivalence provides a simple method to estimate the ridge penalty parameter in comparison to other computationally-demanding estimation approaches based on cross-validation schemes. We evaluated the proposed test using simulation studies and applied it to real data from the Baependi Heart Study consisting of 76 families. Using our approach, we identified an interaction between BMI and the Peroxisome Proliferator Activated Receptor Gamma (PPARG) gene associated with diabetes.
Original language | English (US) |
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Article number | 1134 |
Journal | International journal of environmental research and public health |
Volume | 14 |
Issue number | 10 |
DOIs | |
State | Published - Sep 27 2017 |
Keywords
- Best linear unbiased predictor
- Family data
- Gene-environment interaction
- Generalized linear mixed model
- Ridge regression
- Score test
- Variance component test
ASJC Scopus subject areas
- Pollution
- Public Health, Environmental and Occupational Health
- Health, Toxicology and Mutagenesis