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Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder. / Rajagopal, Veera M; Duan, Jinjie; Vilar-Ribó, Laura et al.
I: Nature Genetics, Bind 54, Nr. 8, 08.2022, s. 1117-1124.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

Harvard

Rajagopal, VM, Duan, J, Vilar-Ribó, L, Grove, J, Zayats, T, Ramos-Quiroga, JA, Satterstrom, FK, Artigas, MS, Bybjerg-Grauholm, J, Bækvad-Hansen, M, Als, TD, Rosengren, A, Daly, MJ, Neale, BM, Nordentoft, M, Werge, T, Mors, O, Hougaard, DM, Mortensen, PB, Ribasés, M, Børglum, AD & Demontis, D 2022, 'Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder', Nature Genetics, bind 54, nr. 8, s. 1117-1124. https://doi.org/10.1038/s41588-022-01143-7

APA

Rajagopal, V. M., Duan, J., Vilar-Ribó, L., Grove, J., Zayats, T., Ramos-Quiroga, J. A., Satterstrom, F. K., Artigas, M. S., Bybjerg-Grauholm, J., Bækvad-Hansen, M., Als, T. D., Rosengren, A., Daly, M. J., Neale, B. M., Nordentoft, M., Werge, T., Mors, O., Hougaard, D. M., Mortensen, P. B., ... Demontis, D. (2022). Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder. Nature Genetics, 54(8), 1117-1124. https://doi.org/10.1038/s41588-022-01143-7

CBE

Rajagopal VM, Duan J, Vilar-Ribó L, Grove J, Zayats T, Ramos-Quiroga JA, Satterstrom FK, Artigas MS, Bybjerg-Grauholm J, Bækvad-Hansen M, et al. 2022. Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder. Nature Genetics. 54(8):1117-1124. https://doi.org/10.1038/s41588-022-01143-7

MLA

Rajagopal, Veera M et al. "Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder". Nature Genetics. 2022, 54(8). 1117-1124. https://doi.org/10.1038/s41588-022-01143-7

Vancouver

Rajagopal VM, Duan J, Vilar-Ribó L, Grove J, Zayats T, Ramos-Quiroga JA et al. Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder. Nature Genetics. 2022 aug.;54(8):1117-1124. doi: 10.1038/s41588-022-01143-7

Author

Rajagopal, Veera M ; Duan, Jinjie ; Vilar-Ribó, Laura et al. / Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder. I: Nature Genetics. 2022 ; Bind 54, Nr. 8. s. 1117-1124.

Bibtex

@article{efe74a6ef3fd4270b790445a4ed76aa7,
title = "Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder",
abstract = "Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n = 14,878), persistent (n = 1,473) and late-diagnosed (n = 6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups. Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD and the highest burden of rare protein-truncating variants in evolutionarily constrained genes. Late-diagnosed ADHD had a larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants. Overall, these results suggest a genetic influence on age at first ADHD diagnosis, persistence of ADHD and the different comorbidity patterns among the groups.",
keywords = "Adult, Attention Deficit Disorder with Hyperactivity/diagnosis, Comorbidity, Genetic Predisposition to Disease, Humans, Multifactorial Inheritance, Neurodevelopmental Disorders",
author = "Rajagopal, {Veera M} and Jinjie Duan and Laura Vilar-Rib{\'o} and Jakob Grove and Tetyana Zayats and Ramos-Quiroga, {J Antoni} and Satterstrom, {F Kyle} and Artigas, {Mar{\'i}a Soler} and Jonas Bybjerg-Grauholm and Marie B{\ae}kvad-Hansen and Als, {Thomas D} and Anders Rosengren and Daly, {Mark J} and Neale, {Benjamin M} and Merete Nordentoft and Thomas Werge and Ole Mors and Hougaard, {David M} and Mortensen, {Preben B} and Marta Ribas{\'e}s and B{\o}rglum, {Anders D} and Ditte Demontis",
note = "{\textcopyright} 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = aug,
doi = "10.1038/s41588-022-01143-7",
language = "English",
volume = "54",
pages = "1117--1124",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "8",

}

RIS

TY - JOUR

T1 - Differences in the genetic architecture of common and rare variants in childhood, persistent and late-diagnosed attention-deficit hyperactivity disorder

AU - Rajagopal, Veera M

AU - Duan, Jinjie

AU - Vilar-Ribó, Laura

AU - Grove, Jakob

AU - Zayats, Tetyana

AU - Ramos-Quiroga, J Antoni

AU - Satterstrom, F Kyle

AU - Artigas, María Soler

AU - Bybjerg-Grauholm, Jonas

AU - Bækvad-Hansen, Marie

AU - Als, Thomas D

AU - Rosengren, Anders

AU - Daly, Mark J

AU - Neale, Benjamin M

AU - Nordentoft, Merete

AU - Werge, Thomas

AU - Mors, Ole

AU - Hougaard, David M

AU - Mortensen, Preben B

AU - Ribasés, Marta

AU - Børglum, Anders D

AU - Demontis, Ditte

N1 - © 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.

PY - 2022/8

Y1 - 2022/8

N2 - Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n = 14,878), persistent (n = 1,473) and late-diagnosed (n = 6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups. Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD and the highest burden of rare protein-truncating variants in evolutionarily constrained genes. Late-diagnosed ADHD had a larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants. Overall, these results suggest a genetic influence on age at first ADHD diagnosis, persistence of ADHD and the different comorbidity patterns among the groups.

AB - Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with onset in childhood (childhood ADHD); two-thirds of affected individuals continue to have ADHD in adulthood (persistent ADHD), and sometimes ADHD is diagnosed in adulthood (late-diagnosed ADHD). We evaluated genetic differences among childhood (n = 14,878), persistent (n = 1,473) and late-diagnosed (n = 6,961) ADHD cases alongside 38,303 controls, and rare variant differences in 7,650 ADHD cases and 8,649 controls. We identified four genome-wide significant loci for childhood ADHD and one for late-diagnosed ADHD. We found increased polygenic scores for ADHD in persistent ADHD compared with the other two groups. Childhood ADHD had higher genetic overlap with hyperactivity and autism compared with late-diagnosed ADHD and the highest burden of rare protein-truncating variants in evolutionarily constrained genes. Late-diagnosed ADHD had a larger genetic overlap with depression than childhood ADHD and no increased burden in rare protein-truncating variants. Overall, these results suggest a genetic influence on age at first ADHD diagnosis, persistence of ADHD and the different comorbidity patterns among the groups.

KW - Adult

KW - Attention Deficit Disorder with Hyperactivity/diagnosis

KW - Comorbidity

KW - Genetic Predisposition to Disease

KW - Humans

KW - Multifactorial Inheritance

KW - Neurodevelopmental Disorders

U2 - 10.1038/s41588-022-01143-7

DO - 10.1038/s41588-022-01143-7

M3 - Journal article

C2 - 35927488

VL - 54

SP - 1117

EP - 1124

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 8

ER -