Genotype-environment interplay in associations between maternal drinking and offspring emotional and behavioral problems.

BACKGROUND: While maternal at-risk drinking is associated with children's emotional and behavioral problems, there is a paucity of research that properly accounts for genetic confounding and gene-environment interplay. Therefore, it remains uncertain what mechanisms underlie these associations. We assess the moderation of associations between maternal at-risk drinking and childhood emotional and behavioral problems by common genetic variants linked to environmental sensitivity (genotype-environment [G × E] interaction) while accounting for shared genetic risk between mothers and offspring (G × E correlation).

METHODS: We use data from 109 727 children born to 90 873 mothers enrolled in the Norwegian Mother, Father, and Child Cohort Study. Women self-reported alcohol consumption and reported emotional and behavioral problems when children were 1.5/3/5 years old. We included child polygenic scores (PGSs) for traits linked to environmental sensitivity as moderators.

RESULTS: Associations between maternal drinking and child emotional ( β 1 = 0.04 [95% confidence interval (CI) 0.03-0.05]) and behavioral ( β 1 = 0.07 [0.06-0.08]) outcomes attenuated after controlling for measured confounders and were almost zero when we accounted for unmeasured confounding (emotional: β 1 = 0.01 [0.00-0.02]; behavioral: β 1 = 0.01 [0.00-0.02]). We observed no moderation of these adjusted exposure effects by any of the PGS.

CONCLUSIONS: The lack of strong evidence for G × E interaction may indicate that the mechanism is not implicated in this kind of intergenerational association. It may also reflect insufficient power or the relatively benign nature of the exposure in this sample.