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Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups.

Authors :
Mattheisen M
Grove J
Als TD
Martin J
Voloudakis G
Meier S
Demontis D
Bendl J
Walters R
Carey CE
Rosengren A
Strom NI
Hauberg ME
Zeng B
Hoffman G
Zhang W
Bybjerg-Grauholm J
Bækvad-Hansen M
Agerbo E
Cormand B
Nordentoft M
Werge T
Mors O
Hougaard DM
Buxbaum JD
Faraone SV
Franke B
Dalsgaard S
Mortensen PB
Robinson EB
Roussos P
Neale BM
Daly MJ
Børglum AD
Source :
Nature genetics [Nat Genet] 2022 Oct; Vol. 54 (10), pp. 1470-1478. Date of Electronic Publication: 2022 Sep 26.
Publication Year :
2022

Abstract

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are highly heritable neurodevelopmental conditions, with considerable overlap in their genetic etiology. We dissected their shared and distinct genetic etiology by cross-disorder analyses of large datasets. We identified seven loci shared by the disorders and five loci differentiating them. All five differentiating loci showed opposite allelic directions in the two disorders and significant associations with other traits, including educational attainment, neuroticism and regional brain volume. Integration with brain transcriptome data enabled us to identify and prioritize several significantly associated genes. The shared genomic fraction contributing to both disorders was strongly correlated with other psychiatric phenotypes, whereas the differentiating portion was correlated most strongly with cognitive traits. Additional analyses revealed that individuals diagnosed with both ASD and ADHD were double-loaded with genetic predispositions for both disorders and showed distinctive patterns of genetic association with other traits compared with the ASD-only and ADHD-only subgroups. These results provide insights into the biological foundation of the development of one or both conditions and of the factors driving psychopathology discriminatively toward either ADHD or ASD.<br /> (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Details

Language :
English
ISSN :
1546-1718
Volume :
54
Issue :
10
Database :
MEDLINE
Journal :
Nature genetics
Publication Type :
Academic Journal
Accession number :
36163277
Full Text :
https://doi.org/10.1038/s41588-022-01171-3