A variance quantitative trait loci map of childhood behaviour: searching for gene-environment interactions in the MoBa cohort

Gene-environment interaction is likely to contribute to human development, but individual effects are difficult to detect, especially for behavioural outcomes. Genetic variants with heteroscedastic effects are potential candidates for tests of interaction. We used item response theory models to reduce measurement error in 71 behavioural traits across childhood (ages 6 months - 14 years) in the Norwegian Mother, Father and Child Birth Cohort Study (MoBa; NMEAN: 31,614) and subsequently tested for genome-wide association (GWA) of mean and variance effects. Downstream analyses included phenome-wide association analyses of independently associated loci, estimation of SNP-based heritability and genetic correlation, and polygenic score analysis in an independent sample, the Twins Early Development Study (NMEAN=1,837). All analyses were repeated in anthropometric traits, to compare with analyses of behaviour. Across the 71 behavioural phenotypes, there were 17 independent genetic variants associated with phenotypic variability, and 44 associated with mean levels. Genome-wide variance effects explained up to 9.7% of the variance (mean h2vGWA=1.8%), whereas mean effects explained up to 15.8% of the phenotypic variance (mean h2GWA=6.0%). In comparison, for anthropometric traits variance effects explained up to 6.7% of the variance in phenotypic variability (mean h2vGWA=2.1%), and mean effects explained up to 42.7% of the phenotypic variance (mean h2GWA=30.5%). There was little evidence that higher variance-based polygenic scores were associated with greater phenotypic variance, or for vPGS-by-environment interactions. In keeping with previous analyses of genetic effects on trait variability in anthropometric and biomarker traits, there were fewer variance effects than mean effects for behavioural traits. However, several SNPs with effects on behavioural phenotypic variance were identified for follow-up analyses. We have provided an extensive summary of the phenotypes assessed in MoBa accompanied by GWA summary statistics made available for future GWA meta-analyses of childhood behavioural traits.