Genetic nurture versus genetic transmission of risk for ADHD traits in the Norwegian Mother, Father and Child Cohort Study

Abstract

Identifying mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) traits can inform interventions and provide insights into the role of parents in shaping their children’s outcomes. We investigated whether genetic transmission and genetic nurture (environmentally mediated effects) underlie associations between polygenic scores indexing parental risk and protective factors and their offspring’s ADHD traits. This birth cohort study included 19,506 genotyped mother-father-offspring trios from the Norwegian Mother, Father and Child Cohort Study. Polygenic scores were calculated for parental factors previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment, and cognitive performance. Mothers reported on their 8-year-old children’s ADHD traits (n = 9,454 children) using the Parent/Teacher Rating Scale for Disruptive Behaviour Disorders. We found that associations between ADHD maternal and paternal polygenic scores and child ADHD traits decreased significantly when adjusting for the child polygenic score (pΔβ = 9.95 × 10−17 for maternal and pΔβ = 1.48 × 10−14 for paternal estimates), suggesting genetic transmission of ADHD risk. Similar patterns suggesting genetic transmission of risk were observed for smoking, educational attainment, and cognition. The maternal polygenic score for neuroticism remained associated with children’s ADHD ratings even after adjusting for the child polygenic score, indicating genetic nurture. There was no robust evidence of genetic nurture for other parental factors. Our findings indicate that the intergenerational transmission of risk for ADHD traits is largely explained by the transmission of genetic variants from parents to offspring rather than by genetic nurture. Observational associations between parental factors and childhood ADHD outcomes should not be interpreted as evidence for predominantly environmentally mediated effects.

Parental personality and early life ecology: a prospective cohort study from preconception to postpartum

“…Such intergenerational continuities could reflect a genetic biological inheritance 50 . Alternatively, evidence from animal and genetically-informed human studies 51 , 52 suggests a social pathway from parental genetic influences via parental characteristics, behaviour and resources that shape children’s development (genetic nurture) 51 , 53 . Consistent with this idea, we found positive associations between parent extraversion and infant approach (reflecting infant comfort in engaging with people and their environment), as well as many parental and contextual attributes that may influence infant approach (e.g., parental mental health, warmth, confidence, and supportive social context) 54 .…”

Predicting childhood ADHD-linked symptoms from prenatal and perinatal data in the ABCD cohort

“…The association between maternal smoking and ADHD in the child appears to be strongly confounded by familial factors and may not be causal (Rice et al, 2018;Thapar et al, 2009). The same concerns may extend to drug-use (Pingault et al, 2022). However, the issue of causality does not necessarily invalidate the predictiveness of these variables.…”

“…Parents with mental health issues may have difficulty attending to their child's needs (Dubber et al, 2015), and may be more likely to be substance users pre-and postnatally (Smedberg et al, 2015). Recent studies have suggested that the effects of environmental factors on ADHD risk may be largely captured by genetic transmission of risk from parents (Agnew-Blais et al, 2022;Pingault et al, 2022). Future studies should use intergenerational Mendelian randomization to test whether associations between pre/perinatal factors are independent from such genetic processes.…”

Causal inference methods for intergenerational research using observational data.

“…If parental nontransmitted genes are associated with the child phenotype (i.e., ruling out genetic transmission), this effect may occur through the parental environment (Bates et al, 2018; Kong et al, 2018). Genetic nurture effects have been examined recently to investigate associations between parental genotype and offspring educational and mental health outcomes (Jami et al, 2020; Pingault, Barkhuizen, et al, 2022; Wang et al, 2021). Figure 4 is an extension of Figure 3 and additionally includes environmental parent-to-offspring effects.…”