Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups. / Mattheisen, Manuel; Grove, Jakob; Als, Thomas D.; Martin, Joanna; Voloudakis, Georgios; Meier, Sandra; Demontis, Ditte; Bendl, Jaroslav; Walters, Raymond; Carey, Caitlin E.; Rosengren, Anders; Strom, Nora I.; Hauberg, Mads Engel; Zeng, Biao; Hoffman, Gabriel; Zhang, Wen; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Agerbo, Esben; Cormand, Bru; Nordentoft, Merete; Werge, Thomas; Mors, Ole; Hougaard, David M.; Buxbaum, Joseph D.; Faraone, Stephen V.; Franke, Barbara; Dalsgaard, Søren; Mortensen, Preben B.; Robinson, Elise B.; Roussos, Panos; Neale, Benjamin M.; Daly, Mark J.; Børglum, Anders D.
I: Nature Genetics, Bind 54, 2022, s. 1470–1478 .Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups
AU - Mattheisen, Manuel
AU - Grove, Jakob
AU - Als, Thomas D.
AU - Martin, Joanna
AU - Voloudakis, Georgios
AU - Meier, Sandra
AU - Demontis, Ditte
AU - Bendl, Jaroslav
AU - Walters, Raymond
AU - Carey, Caitlin E.
AU - Rosengren, Anders
AU - Strom, Nora I.
AU - Hauberg, Mads Engel
AU - Zeng, Biao
AU - Hoffman, Gabriel
AU - Zhang, Wen
AU - Bybjerg-Grauholm, Jonas
AU - Bækvad-Hansen, Marie
AU - Agerbo, Esben
AU - Cormand, Bru
AU - Nordentoft, Merete
AU - Werge, Thomas
AU - Mors, Ole
AU - Hougaard, David M.
AU - Buxbaum, Joseph D.
AU - Faraone, Stephen V.
AU - Franke, Barbara
AU - Dalsgaard, Søren
AU - Mortensen, Preben B.
AU - Robinson, Elise B.
AU - Roussos, Panos
AU - Neale, Benjamin M.
AU - Daly, Mark J.
AU - Børglum, Anders D.
N1 - Publisher Copyright: © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s41588-022-01171-3
DO - 10.1038/s41588-022-01171-3
M3 - Journal article
C2 - 36163277
AN - SCOPUS:85138743007
VL - 54
SP - 1470
EP - 1478
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
ER -
ID: 321706231