The nature of nurture: a genomewide association scan for family chaos

Widely used measures of the environment, especially the family environment of children, show genetic influence in dozens of twin and adoption studies. This phenomenon is known as gene-environment correlation in which genetically driven influences of individuals affect their environments. We conducted the first genome-wide association (GWA) analysis of an environmental measure. We used a measure called CHAOS which assesses 'environmental confusion' in the home, a measure that is more strongly associated with cognitive development in childhood than any other environmental measure. CHAOS was assessed by parental report when the children were 3 years and again when the children were 4 years; a composite CHAOS measure was constructed across the 2 years. We screened 490,041 autosomal single-nucleotide polymorphisms (SNPs) in a two-stage design in which children in low chaos families (N = 469) versus high chaos families (N = 369) from 3,000 families of 4-year-old twins were screened in Stage 1 using pooled DNA. In Stage 2, following SNP quality control procedures, 41 nominated SNPs were tested for association with family chaos by individual genotyping an independent representative sample of 3,529. Despite having 99% power to detect associations that account for more than 0.5% of the variance, none of the 41 nominated SNPs met conservative criteria for replication. Similar to GWA analyses of other complex traits, it is likely that most of the heritable variation in environmental measures such as family chaos is due to many genes of very small effect size.