Abstract
Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly heritable neurodevelopmental disorders that frequently co-occur. Both rare and common genetic variants are important for ASD and ADHD risk but their combined contribution to clinical heterogeneity is unclear. In a sample of 39 ASD and/or ADHD families we estimated the overall variance explained by known rare copy number variants (CNVs) and polygenic risk score (PRS) from common variants to be 10% in comorbid ASD/ADHD, 4% in ASD and 2% in ADHD. We show that burden of large, rare CNVs and PRS is significantly higher in adult ASD and/or ADHD patients with sustained need for specialist care compared to their unaffected relatives, while affected relatives fall in-between the two.
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The research leading to these results has received funding from The Lundbeck Foundation No R208-2015-3951 and Fonden for Faglig Udvikling af Speciallægepraksis No 38850/16.
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SLB contributed to collecting and analysing data, manuscript writing. JLB, KDJ and AKP participated in the supervising data collection. VA conceived the polygenic risk score implementation. AB and TW contributed to supervising data analysis and manuscript writing.
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Thomas Werge has served as a lecturer for and consultant to H. Lundbeck A/S. Jette LaBianca has served at the advisory board for H. Lundbeck A/S and as lecturer for H. Lundbeck A/S, Shire and Servier. Klaus Damgaard Jakobsen has been a consultant for AstraZeneca, on advisory board for Bristol Myers Squibb and received speaker's honoraria from Lundbeck Pharma. Anne Katrine Pagsberg, Vivek Appadurai, Alfonso Buil and Sonja LaBianca report no conflicts of interest.
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LaBianca, S., LaBianca, J., Pagsberg, A.K. et al. Copy Number Variants and Polygenic Risk Scores Predict Need of Care in Autism and/or ADHD Families. J Autism Dev Disord 51, 276–285 (2021). https://doi.org/10.1007/s10803-020-04552-x
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DOI: https://doi.org/10.1007/s10803-020-04552-x