Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD

Trine Tollerup Nielsen; Jinjie Duan; Daniel F. Levey; G. Bragi Walters; Emma C. Johnson; Thorgeir Thorgeirsson; Joel Gelernter; Daniel F. Levey; Thomas Werge; Preben Bo Mortensen; Hreinn Stefansson; Kari Stefansson; David M. Hougaard; Arpana Agrawal; Joel Gelernter; Jakob Grove; Anders D. Børglum; Ditte Demontis; VA Million Veteran Program

doi:10.1038/s44220-024-00277-3

Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD

Trine Tollerup Nielsen, Jinjie Duan, Daniel F. Levey, G. Bragi Walters, Emma C. Johnson, Thorgeir Thorgeirsson, Joel Gelernter, Daniel F. Levey, Thomas Werge, Preben Bo Mortensen, Hreinn Stefansson, Kari Stefansson, David M. Hougaard, Arpana Agrawal, Joel Gelernter, Jakob Grove, Anders D. Børglum, Ditte Demontis^*, VA Million Veteran Program

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

1 Citationer (Scopus)

Abstract

Cannabis use disorder (CUD) and cannabis use (CU) are prevalent conditions co-occurring with attention-deficit hyperactivity disorder (ADHD). Here we report results from a cross-disorder genome-wide association study of ADHD and CUD or CU. We identified 36 concordant genome-wide significant loci for ADHD–CUD and ten loci for ADHD–CU. DRD2 was identified as an ADHD–CUD risk gene. ADHD–CUD risk genes showed high expression across brain tissues and brain developmental stages, which was not observed for ADHD–CU genes. ADHD–CUD and ADHD–CU showed similar genetic correlations with substance use, whereas they differed for substance-use disorders. Individuals with ADHD–CUD had increased polygenic scores (PGS) for psychiatric disorders compared with those with ADHD without CUD and increased burden of rare deleterious variants. Stratification of individuals with ADHD by their CUD PGS revealed an absolute risk of 22% for comorbid CUD in the highest CUD-PGS bin—much higher than 1.6% risk among controls. Sex-specific differences were substantial with an approximately 10% higher CUD risk among men in the highest CUD-PGS bin.

Originalsprog	Engelsk
Artikelnummer	108535
Tidsskrift	Nature Mental Health
Vol/bind	2
Udgave nummer	9
Sider (fra-til)	1071-1083
Antal sider	13
DOI	https://doi.org/10.1038/s44220-024-00277-3
Status	Udgivet - 2024
Udgivet eksternt	Ja

Bibliografisk note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.

Adgang til dokumentet

10.1038/s44220-024-00277-3

Biblioteksadgang?

Tjek tilgængelighed hos det Kgl. Bibliotek

Citationsformater

Nielsen, T. T., Duan, J., Levey, D. F., Walters, G. B., Johnson, E. C., Thorgeirsson, T., Gelernter, J., Levey, D. F., Werge, T., Mortensen, P. B., Stefansson, H., Stefansson, K., Hougaard, D. M., Agrawal, A., Gelernter, J., Grove, J., Børglum, A. D., Demontis, D., & VA Million Veteran Program (2024). Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD. Nature Mental Health, 2(9), 1071-1083. Artikel 108535. https://doi.org/10.1038/s44220-024-00277-3

Nielsen, TT, Duan, J, Levey, DF, Walters, GB, Johnson, EC, Thorgeirsson, T, Gelernter, J, Levey, DF, Werge, T, Mortensen, PB, Stefansson, H, Stefansson, K, Hougaard, DM, Agrawal, A, Gelernter, J, Grove, J, Børglum, AD, Demontis, D & VA Million Veteran Program 2024, 'Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD', Nature Mental Health, bind 2, nr. 9, 108535, s. 1071-1083. https://doi.org/10.1038/s44220-024-00277-3

@article{3d49f3a91f064294b526ee2633ef82e3,

title = "Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD",

abstract = "Cannabis use disorder (CUD) and cannabis use (CU) are prevalent conditions co-occurring with attention-deficit hyperactivity disorder (ADHD). Here we report results from a cross-disorder genome-wide association study of ADHD and CUD or CU. We identified 36 concordant genome-wide significant loci for ADHD–CUD and ten loci for ADHD–CU. DRD2 was identified as an ADHD–CUD risk gene. ADHD–CUD risk genes showed high expression across brain tissues and brain developmental stages, which was not observed for ADHD–CU genes. ADHD–CUD and ADHD–CU showed similar genetic correlations with substance use, whereas they differed for substance-use disorders. Individuals with ADHD–CUD had increased polygenic scores (PGS) for psychiatric disorders compared with those with ADHD without CUD and increased burden of rare deleterious variants. Stratification of individuals with ADHD by their CUD PGS revealed an absolute risk of 22% for comorbid CUD in the highest CUD-PGS bin—much higher than 1.6% risk among controls. Sex-specific differences were substantial with an approximately 10% higher CUD risk among men in the highest CUD-PGS bin.",

author = "Nielsen, {Trine Tollerup} and Jinjie Duan and Levey, {Daniel F.} and Walters, {G. Bragi} and Johnson, {Emma C.} and Thorgeir Thorgeirsson and Joel Gelernter and Levey, {Daniel F.} and Thomas Werge and Mortensen, {Preben Bo} and Hreinn Stefansson and Kari Stefansson and Hougaard, {David M.} and Arpana Agrawal and Joel Gelernter and Jakob Grove and B{\o}rglum, {Anders D.} and Ditte Demontis and {VA Million Veteran Program}",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.",

year = "2024",

doi = "10.1038/s44220-024-00277-3",

language = "English",

volume = "2",

pages = "1071--1083",

journal = "Nature Mental Health",

issn = "2731-6076",

publisher = "Nature Research",

number = "9",

}

TY - JOUR

T1 - Shared genetics of ADHD, cannabis use disorder and cannabis use and prediction of cannabis use disorder in ADHD

AU - Nielsen, Trine Tollerup

AU - Duan, Jinjie

AU - Levey, Daniel F.

AU - Walters, G. Bragi

AU - Johnson, Emma C.

AU - Thorgeirsson, Thorgeir

AU - Gelernter, Joel

AU - Levey, Daniel F.

AU - Werge, Thomas

AU - Mortensen, Preben Bo

AU - Stefansson, Hreinn

AU - Stefansson, Kari

AU - Hougaard, David M.

AU - Agrawal, Arpana

AU - Gelernter, Joel

AU - Grove, Jakob

AU - Børglum, Anders D.

AU - Demontis, Ditte

AU - VA Million Veteran Program

PY - 2024

Y1 - 2024

N2 - Cannabis use disorder (CUD) and cannabis use (CU) are prevalent conditions co-occurring with attention-deficit hyperactivity disorder (ADHD). Here we report results from a cross-disorder genome-wide association study of ADHD and CUD or CU. We identified 36 concordant genome-wide significant loci for ADHD–CUD and ten loci for ADHD–CU. DRD2 was identified as an ADHD–CUD risk gene. ADHD–CUD risk genes showed high expression across brain tissues and brain developmental stages, which was not observed for ADHD–CU genes. ADHD–CUD and ADHD–CU showed similar genetic correlations with substance use, whereas they differed for substance-use disorders. Individuals with ADHD–CUD had increased polygenic scores (PGS) for psychiatric disorders compared with those with ADHD without CUD and increased burden of rare deleterious variants. Stratification of individuals with ADHD by their CUD PGS revealed an absolute risk of 22% for comorbid CUD in the highest CUD-PGS bin—much higher than 1.6% risk among controls. Sex-specific differences were substantial with an approximately 10% higher CUD risk among men in the highest CUD-PGS bin.

AB - Cannabis use disorder (CUD) and cannabis use (CU) are prevalent conditions co-occurring with attention-deficit hyperactivity disorder (ADHD). Here we report results from a cross-disorder genome-wide association study of ADHD and CUD or CU. We identified 36 concordant genome-wide significant loci for ADHD–CUD and ten loci for ADHD–CU. DRD2 was identified as an ADHD–CUD risk gene. ADHD–CUD risk genes showed high expression across brain tissues and brain developmental stages, which was not observed for ADHD–CU genes. ADHD–CUD and ADHD–CU showed similar genetic correlations with substance use, whereas they differed for substance-use disorders. Individuals with ADHD–CUD had increased polygenic scores (PGS) for psychiatric disorders compared with those with ADHD without CUD and increased burden of rare deleterious variants. Stratification of individuals with ADHD by their CUD PGS revealed an absolute risk of 22% for comorbid CUD in the highest CUD-PGS bin—much higher than 1.6% risk among controls. Sex-specific differences were substantial with an approximately 10% higher CUD risk among men in the highest CUD-PGS bin.

U2 - 10.1038/s44220-024-00277-3

DO - 10.1038/s44220-024-00277-3

M3 - Journal article

AN - SCOPUS:85218256097

SN - 2731-6076

VL - 2

SP - 1071

EP - 1083

JO - Nature Mental Health

JF - Nature Mental Health

IS - 9

M1 - 108535

ER -