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

ended

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 preventive interventions. Parental risk factors –e.g. psychiatric disorders and substance use– have consistently emerged as strong predictors of child psychiatric symptoms. However, we do not know whether such parental risk factors are causes or mere correlates of child symptoms and how this transmission of risk across generations occurs. The overarching aim of I-RISK is to identify causal intergenerational pathways linking parental risk factors to child psychiatric symptoms. I-RISK will implement and develop cutting-edge genetically informed methods to enable better causal inference in intergenerational research. Three work packages will address major limitations in state-of-the-art research: (i) no study to date has applied such causal inference methods to identify intergenerational risk factors for child psychiatric symptoms; (ii) the role of intermediate phenotypes, whether environmental (e.g. parenting) or biological (epigenetic and brain data), in explaining the intergenerational transmission of risk remains poorly understood; (iii) genetically informed intergenerational research is still in its infancy and key methodological developments are required to propel the field forward. I-RISK will generate new genomic data and bring together four of the largest child cohorts in Europe (pooled N >100,000). These cohorts feature genetic data in children and parents as well as unique data on environmental and biological intermediate phenotypes. I-RISK will pioneer a paradigm shift in intergenerational mental health research and provide unprecedented insights into the aetiology of child psychiatric symptoms, with the ultimate goal of breaking the intergenerational cycle of mental illness and inequalities.