LEGENNDS: Linking Epidemiology and GEnetics of Neurodevelopmental and Neurodegenerative Disorders Study

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Project Abstract Emerging evidence suggests that certain neurodevelopmental disorders – autism (ASD), attention-deficit hyperactive disorder (ADHD), and intellectual disability (ID) – may increase risk of later life neurodegenerative disorders such as Alzheimer’s disease or related dementia (ADRD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). We propose a multinational study of epidemiological and genetic data across the countries of Sweden, Denmark, and the UK to characterize the natural history (Aim 1) and familial aggregation (Aim 2) of these disorders. We also explore genetic links (Aim 3) between neurodevelopmental and later life neurodegenerative disorders, and identify potential targets for intervention that may mitigate risk (Aim 4). Our study will use data from 10+ million persons from Sweden and Denmark with decades of follow-up; iPSYCH, an extensively genotyped case-cohort with ~25,000 ASD, ~30,000 ADHD cases, and 50,000 controls; and a prospective cohort of older adults from the UK (UK Biobank) totaling over half a million persons. Our analytic approach links epidemiological and genetic data, that together, triangulate to answer the question of whether ASD, ADHD, and ID increase risk of ADRD, PD, and ALS.