From parental risk to child mental illness: a genetically informed investigation of intergenerational risk pathways

Informations projet

I-RISK

N° de convention de subvention: 863981

DOI

10.3030/863981

Projet clôturé

Date de signature de la CE 24 Avril 2020

Date de début 1 Juin 2020

Date de fin 30 Novembre 2025

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 2 183 293,00

Contribution de l’UE

€ 2 183 293,00

Coordonné par

UNIVERSITY COLLEGE LONDON
United Kingdom

Periodic Reporting for period 3 - I-RISK (From parental risk to child mental illness: a genetically informed investigation of intergenerational risk pathways)

Période du rapport: 2023-06-01 au 2024-11-30

Résumé du contexte et des objectifs généraux du projet

Mental illnesses account for 32% of years lived with disability. Critically, 50% of mental illnesses are established before age 14 years. It is thus imperative to better understand the causes of early psychiatric symptoms in childhood if we are to design effective interventions. Parental risk factors –e.g. psychiatric disorders and substance use– are strong predictors of child psychiatric symptoms. However, we do not know whether such parental risk factors are causes or simple correlates of child symptoms and how this transmission of risk across generations occurs. This is important because if a risk factor is not causal, then intervening on this risk factor will not change the outcome. A better understanding of how risk for mental illness is transmitted across generation would help us understand how to best prevent this transmission of risk to children, with the ultimate goal of breaking the intergenerational cycle of mental illness and inequalities.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Halfway through the project, we are starting to get a better understanding of how psychiatric risk is transmitted across generations. We have been conducting work in large cohort studies, such as the Norwegian Mother, Father and Child Cohort Study (MoBa), which follows thousands of children from early childhood to adulthood. A characteristic of MoBa is that it contains genotyped trios, i.e. mother/father/child trios for which we have genomic information. With the genomic data, we create polygenic scores, which provide an individual index of the genetic risk for a given condition, for example Attention-Deficit Hyperactivity Disorders. We then use those polygenic scores for each of the mother, father and child to better understand the role of genetics in the intergenerational transmission of risk. Our first results show that when focusing on the intergenerational transmission of ADHD, it appears that a large part is due to genetic transmission rather than to an environmental pathway (e.g. parental ADHD affects parenting practices, which in turn affects child ADHD).

We have also been conducting methodological work aimed at better integrating polygenic risk scores to cohort studies. This is because integrating such scores comes with many challenges, which must be acknowledged to avoid biased results.

Results from these two lines of work have been published in scientific journals.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

The results that we have published so far are novel and beyond the state of the art. This was the first time that genotyped trios were used in a large sample to better understand the transmission of ADHD. And our methodological work is also beyond the state of the art and provides researchers with the theoretical framework and software to better integrate polygenic scores in their studies. Such methods are applicable beyond the field of mental health research.

Until the end of the project, we first expect to generalise our finding regarding ADHD to other childhood outcomes. After understanding how much genetic transmission and environmental factors respectively play a role in the intergenerational transmission of risk for mental health, we will focus on a more granular understanding of those transmission pathways. In particular, we will look at the role of environmental variables (e.g. parenting) and biological variables (e.g. epigenetics) in this intergenerational transmission of risk. We will also conduct further methodological work to generalise our early findings and make our software applicable to more questions in mental health research and beyond.

I-RISK Description