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

Project Information

I-RISK

Grant agreement ID: 863981

DOI

10.3030/863981

Project closed

EC signature date 24 April 2020

Start date 1 June 2020

End date 30 November 2025

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 2 183 293,00

EU contribution

€ 2 183 293,00

Coordinated by

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)

Reporting period: 2023-06-01 to 2024-11-30

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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