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

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

In: Nature Genetics, Vol. 54, 2022, p. 1470–1478 .

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

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 2022, 'Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups', Nature Genetics, vol. 54, pp. 1470–1478 . https://doi.org/10.1038/s41588-022-01171-3

APA

Mattheisen, M., Grove, J., Als, T. D., Martin, J., Voloudakis, G., Meier, S., Demontis, D., Bendl, J., Walters, R., Carey, C. E., Rosengren, A., Strom, N. I., Hauberg, M. E., Zeng, B., Hoffman, G., Zhang, W., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Agerbo, E., ... Børglum, A. D. (2022). Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups. Nature Genetics, 54, 1470–1478 . https://doi.org/10.1038/s41588-022-01171-3

Vancouver

Mattheisen M, Grove J, Als TD, Martin J, Voloudakis G, Meier S et al. Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups. Nature Genetics. 2022;54:1470–1478 . https://doi.org/10.1038/s41588-022-01171-3

Author

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. / Identification of shared and differentiating genetic architecture for autism spectrum disorder, attention-deficit hyperactivity disorder and case subgroups. In: Nature Genetics. 2022 ; Vol. 54. pp. 1470–1478 .

Bibtex

@article{cf69a54d9dcc424a8c709228c8737e67,

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

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.",

author = "Manuel Mattheisen and Jakob Grove and Als, {Thomas D.} and Joanna Martin and Georgios Voloudakis and Sandra Meier and Ditte Demontis and Jaroslav Bendl and Raymond Walters and Carey, {Caitlin E.} and Anders Rosengren and Strom, {Nora I.} and Hauberg, {Mads Engel} and Biao Zeng and Gabriel Hoffman and Wen Zhang and Jonas Bybjerg-Grauholm and Marie B{\ae}kvad-Hansen and Esben Agerbo and Bru Cormand and Merete Nordentoft and Thomas Werge and Ole Mors and Hougaard, {David M.} and Buxbaum, {Joseph D.} and Faraone, {Stephen V.} and Barbara Franke and S{\o}ren Dalsgaard and Mortensen, {Preben B.} and Robinson, {Elise B.} and Panos Roussos and Neale, {Benjamin M.} and Daly, {Mark J.} and B{\o}rglum, {Anders D.}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2022",

doi = "10.1038/s41588-022-01171-3",

language = "English",

volume = "54",

pages = "1470–1478 ",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "nature publishing group",

}

RIS

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.

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

Department of Clinical Medicine