Detection of gene-environment interaction in pedigree data using genome-wide genotypes

Abstract

Heritability may be estimated using phenotypic data collected in relatives or in distantly related individuals using genome-wide single nucleotide polymorphism (SNP) data. We combined these approaches by re-parameterizing the model proposed by Zaitlen et al and extended this model to include moderation of (total and SNP-based) genetic and environmental variance components by a measured moderator. By means of data simulation, we demonstrated that the type 1 error rates of the proposed test are correct and parameter estimates are accurate. As an application, we considered the moderation by age or year of birth of variance components associated with body mass index (BMI), height, attention problems (AP), and symptoms of anxiety and depression. The genetic variance of BMI was found to increase with age, but the environmental variance displayed a greater increase with age, resulting in a proportional decrease of the heritability of BMI. Environmental variance of height increased with year of birth. The environmental variance of AP increased with age. These results illustrate the assessment of moderation of environmental and genetic effects, when estimating heritability from combined SNP and family data. The assessment of moderation of genetic and environmental variance will enhance our understanding of the genetic architecture of complex traits.

Figure 1

(a) in AP as a function of age. (b) the heritability and proportion of phenotypic variance attributable to SNPs in AP as a function of age. The histogram displays the distribution of the standardized moderator age.

Figure 2

(a) in BMI as a function of age. (b) The heritability and proportion of phenotypic variance attributable to SNPs in BMI as a function of age. The histogram displays the distribution of the standardized moderator age.

Figure 3

(a) in height as a function of birth year. (b) The heritability and proportion of phenotypic variance attributable to SNPs in heigh as a function of birth year. The histogram displays the distribution of the standardized moderator birth year.