Early-life environmental risk factors of Intellectual Disability: biological, psychosocial influences and early identification– Nationwide Twin and Family Study.

Research problem and specific questions: Intellectual disability (ID) affects 2% of children worldwide. The disability is present throughout the lifespan, leading to significant morbidity and premature deaths. Early-life risk factors and low socioeconomic status (SES) are associated with ID.

But the absence of genetically-informative studies prevented researchers from distinguishing between potential causal environmental influences and genetic confounding.

In the proposed project, we will study the effect of early-life environmental factors for ID and identify risk groups in need of clinical follow-up.The aim of this project is to answer the following research questions:What is the causal mechanism by which early-life risk factors are associated with risk of ID?What is the mechanism underlying the association between SES and ID?

Which early-life risk factors mediate this associations?Which risk groups are mostly likely to benefit from targeted pediatric surveillance and early health interventions?Data and method: We will use large-scale longitudinal linkages of administrative and health registers along with the Swedish Twin and Multi-Generation Registers.

We will examine association between exposures to 1) early-life risk factors and 2) low SES with the outcome of ID.

The association will be investigated in the overall population (between-family analyses) and, to address potential causality by adjusting for familial confounding in siblings (i) full-siblings, half-siblings, cousins and (ii) twins (within-family analyses).

We will apply causal inference methods for mediation and interactions. 3) We will develop a Clinical Risk Score for prediction of ID based on early-life risk factors, SES and familial risk score.Plan for project realization: The project will be carried out over three years in close collaboration with reference group involving representatives from self-advocacy group “Grunden and Inre Ringen” and relevant stakeholders such as Young People and Adults with Intellectual Disability (FUB), the National Board of Health and Welfare, the Swedish Agency for Participation and the Swedish Municipalities and Regions (SKR).Relevance: The project will increase our knowledge on modifiable risk factors for ID, crucial for informing prevention in the population.

If we can identify children atrisk of disabilities, we will be able to plan follow-ups and provide the best opportunities for timely diagnosis and early interventions in children and their families.