Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy.
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Authors
Rai, Dheeraj
Publication Date
2021-11-11Journal Title
Nat Commun
ISSN
2041-1723
Publisher
Springer Science and Business Media LLC
Volume
12
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Verhoef, E., Grove, J., Shapland, C. Y., Demontis, D., Burgess, S., Rai, D., Børglum, A. D., & et al. (2021). Discordant associations of educational attainment with ASD and ADHD implicate a polygenic form of pleiotropy.. Nat Commun, 12 (1) https://doi.org/10.1038/s41467-021-26755-1
Abstract
Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) are complex co-occurring neurodevelopmental conditions. Their genetic architectures reveal striking similarities but also differences, including strong, discordant polygenic associations with educational attainment (EA). To study genetic mechanisms that present as ASD-related positive and ADHD-related negative genetic correlations with EA, we carry out multivariable regression analyses using genome-wide summary statistics (N = 10,610-766,345). Our results show that EA-related genetic variation is shared across ASD and ADHD architectures, involving identical marker alleles. However, the polygenic association profile with EA, across shared marker alleles, is discordant for ASD versus ADHD risk, indicating independent effects. At the single-variant level, our results suggest either biological pleiotropy or co-localisation of different risk variants, implicating MIR19A/19B microRNA mechanisms. At the polygenic level, they point to a polygenic form of pleiotropy that contributes to the detectable genome-wide correlation between ASD and ADHD and is consistent with effect cancellation across EA-related regions.
Keywords
Attention Deficit Disorder with Hyperactivity, Autism Spectrum Disorder, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Regression Analysis
Sponsorship
British Heart Foundation (None)
British Heart Foundation (CH/12/2/29428)
British Heart Foundation (RG/18/13/33946)
Wellcome Trust (204623/Z/16/Z)
Medical Research Council (MC_UU_00002/7)
Identifiers
PMC8586371, 34764245
External DOI: https://doi.org/10.1038/s41467-021-26755-1
This record's URL: https://www.repository.cam.ac.uk/handle/1810/332302
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