Direct and indirect effects of maternal, paternal, and offspring genotypes: Trio-GCTA

Eilertsen, Espen Moen; Jami, Eshim S; McAdams, Tom A.; Hannigan, Laurie; Havdahl, Alexandra; Magnus, Per; Evans, David M.; Ystrøm, Eivind

doi:10.1101/2020.05.15.097840

Cited by 14 publications

(17 citation statements)

References 29 publications

(26 reference statements)

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“…31,32 As such, we should not be expecting universal patterns when it comes to explaining the role of intergenerational risk factors in children’s developmental outcomes. Emerging genetically informed methods 26,31,58 should shortly render a detailed depiction of the intergenerational transmission of risk for psychiatric symptoms.…”

Section: Discussionmentioning

confidence: 99%

Identifying intergenerational risk factors for ADHD symptoms using polygenic scores in the Norwegian Mother, Father and Child Cohort

Pingault

Barkhuizen

Wang

et al. 2021

Preprint

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Importance: Knowledge of the mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) symptoms can inform psychosocial interventions. Objective: To investigate whether parental genetic risk factors associate with their children's ADHD symptoms due to genetic transmission of risk or due to parental genetic liability that influences offspring ADHD via parenting environments (genetic nurture). Design and participants: This study is based on the Norwegian Mother, Father and Child Cohort Study and uses data from the Medical Birth Registry of Norway. This prospective cohort study consisted of 5,405 mother-father-offspring trios recruited between 1999 - 2008. Exposures: We calculated polygenic scores for parental traits previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment and intellectual ability. Main outcomes and measures: Mothers reported on their 8-year-old children's ADHD symptoms using the Parent/Teacher Rating Scale for Disruptive Behavior Disorders. Results: Maternal polygenic scores for ADHD, autism spectrum disorder (ASD), neuroticism and smoking predicted child ADHD symptoms in bivariate analyses. After jointly modelling maternal, paternal and child polygenic scores, ADHD symptoms were predicted by children's polygenic scores for ADHD (β = 0.10; 95% CI 0.07 to 0.14), smoking (β = 0.07; 95% CI 0.03 to 0.10) and educational attainment (β = -0.09; 95% CI -0.13 to -0.05), indicating direct genetic transmission of risk. Mothers' polygenic scores for ASD (β = 0.05; 95% CI 0.02 to 0.08) and neuroticism (β = 0.05; 95% CI 0.01 to 0.08) predicted children's ADHD symptoms conditional on fathers' and children's scores, implicating genetic nurture, or effects due to population stratification or assortative mating. Conclusions: These results suggest that associations between some parental traits and offspring ADHD symptoms likely reflect a nuanced mix of direct genetic transmission (ADHD, smoking and educational attainment) and genetic nurture (ASD and neuroticism). If confirmed, these findings support previous evidence that maternal ASD or neuroticism may be possible targets for intervention to help break the chain of the intergenerational transmission of ADHD risk. Keywords: MoBa, attention-deficit/hyperactivity disorder, intergenerational transmission, genetic nurture, parenting.

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Section: Discussionmentioning

confidence: 99%

Identifying intergenerational risk factors for ADHD symptoms using polygenic scores in the Norwegian Mother, Father and Child Cohort

Pingault

Barkhuizen

Wang

et al. 2021

Preprint

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“…It is unknown whether this finding holds for indirect genetic effects, including on childhood educational achievement outcomes. Another gender aspect to consider is differential maternal and paternal indirect genetic effects (Eilertsen et al 2020). There is some evidence (although not genetically informed) that mother and father skills show unique associations with offspring education (Grönqvist et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores

Demange

Hottenga

Abdellaoui

et al. 2020

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Understanding how parents shape their children’s educational trajectories is a socially important research goal. Evidence on the effects of parents’ cognitive and non-cognitive skills on offspring education is weakened by poor assessments of non-cognitive skills and inadequate accounting for genetic inheritance. In this preregistered study, we use genetics to assess non-cognitive skills and to index environmental effects of parents, controlling for direct effects of inherited genetic variation. We define the non-cognitive and cognitive heritable contributions to educational attainment using GWAS-by-subtraction, and construct non-cognitive and cognitive skills polygenic scores in three UK and Dutch cohorts. We estimate environmentally mediated effects of polygenic scores (parental indirect genetic effects) on educational achievement and attainment with three designs that include siblings (N=47,459), adoptees (N=6,407), and parent-offspring trios (N=2,534). Heritable non-cognitive and cognitive skills are both involved in parental construction of environments influencing offspring education: indirect genetic effects explain ∼37% of total polygenic score effects. This result holds across countries, outcomes, ages and methods, with two exceptions: indirect genetic effects are null for childhood achievement in the Dutch cohort, and lower when estimated with the adoption method. Overall, our findings stress the importance of both non-cognitive and cognitive aspects of the home environment.

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“…To obtain estimates of indirect genetic effects using adoption data, genetic associations estimated for adoptees and non-adopted individuals are compared 29 . Notably, variance decomposition as well as PGS methods can be applied to disentangle direct and indirect genetic effects, but the former requires much larger sample sizes [32][33][34][35] . It is not known whether parental indirect genetic effects on offspring education occur through cognitive or non-cognitive pathways (or both), because studies have not parsed out the contributions of subcomponents of the educational attainment PGS.…”

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confidence: 99%

Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores

et al. 2022

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Understanding how parents’ cognitive and non-cognitive skills influence offspring education is essential for educational, family and economic policy. We use genetics (GWAS-by-subtraction) to assess a latent, broad non-cognitive skills dimension. To index parental effects controlling for genetic transmission, we estimate indirect parental genetic effects of polygenic scores on childhood and adulthood educational outcomes, using siblings (N = 47,459), adoptees (N = 6407), and parent-offspring trios (N = 2534) in three UK and Dutch cohorts. We find that parental cognitive and non-cognitive skills affect offspring education through their environment: on average across cohorts and designs, indirect genetic effects explain 36–40% of population polygenic score associations. However, indirect genetic effects are lower for achievement in the Dutch cohort, and for the adoption design. We identify potential causes of higher sibling- and trio-based estimates: prenatal indirect genetic effects, population stratification, and assortative mating. Our phenotype-agnostic, genetically sensitive approach has established overall environmental effects of parents’ skills, facilitating future mechanistic work.

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Direct and indirect effects of maternal, paternal, and offspring genotypes: Trio-GCTA

Cited by 14 publications

References 29 publications

Identifying intergenerational risk factors for ADHD symptoms using polygenic scores in the Norwegian Mother, Father and Child Cohort

Identifying intergenerational risk factors for ADHD symptoms using polygenic scores in the Norwegian Mother, Father and Child Cohort

Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores

Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores

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