A significant role for maternal genetic nurture in the risk architecture of attention-deficit/hyperactivity disorder
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Objective
Previous studies have shown that parental factors are associated with an increased risk for attention-deficit/hyperactivity disorder (ADHD). However, the pathways by which parental factors are associated with risk of ADHD in offspring are not well understood. These associations can arise directly from parental genotypes inherited by offspring, and/or via environmental effects, some of which may themselves be influenced by the parental genotype (i.e., parental genetic nurture). This study specifically examines the impact of the maternal phenotype on offspring ADHD risk, above and beyond the direct genetic effect of maternally-inherited genes.
Methods
The study population consisted of 982,544 individuals from the Swedish Medical Birth Register. We partitioned the liability of ADHD into direct additive genetic effect, maternal genetic nurture effect, and maternal common environment effect.
Results
We identified 66,707 (7%) individuals in the birth cohort with an ADHD diagnosis. Maternal half-siblings were associated with a higher ADHD risk compared to paternal half-siblings, suggesting maternal effect. We estimated 66.1% direct additive genetic effect (95% credible interval, 0.647%-0.676%) and 14.3% maternal genetic nurture effect (95% credible interval, 0.136%-0.151%). Additionally, we also observed evidence for substantial assortative mating among individuals with ADHD.
Conclusions
Our findings indicate that maternal genotypes influence offspring’s risk of ADHD through environmental pathways beyond the effects of direct genetic transmission. Exploring the impact of the genetics of the mother beyond the maternally inherited genes can lead to new insights into ADHD risk. Future studies should also investigate paternal effects to provide a more comprehensive understanding of the ADHD risk architecture.
