Genetic liability to ADHD and substance use disorders in individuals with ADHD

Theresa Wimberley; Esben Agerbo; Henriette Thisted Horsdal; Caecilie Ottosen; Isabell Brikell; Thomas Damm Als; Ditte Demontis; Anders D Børglum; Merete Nordentoft; Ole Mors; Thomas Werge; David Hougaard; Jonas Bybjerg-Grauholm; Marie Baekvad Hansen; Preben Bo Mortensen; Anita Thapar; Lucy Riglin; Kate Langley; Søren Dalsgaard

doi:10.1111/add.14910

Genetic liability to ADHD and substance use disorders in individuals with ADHD

Theresa Wimberley, Esben Agerbo, Henriette Thisted Horsdal, Caecilie Ottosen, Isabell Brikell, Thomas Damm Als, Ditte Demontis, Anders D Børglum, Merete Nordentoft, Ole Mors, Thomas Werge, David Hougaard, Jonas Bybjerg-Grauholm, Marie Baekvad Hansen, Preben Bo Mortensen, Anita Thapar, Lucy Riglin, Kate Langley, Søren Dalsgaard

43 Citationer (Scopus)

Abstract

AIMS: 1) To investigate whether genetic liability to attention-deficit/hyperactivity disorder (ADHD), indexed by polygenic risk scores for ADHD (PRS-ADHD), is associated with substance use disorders (SUD) in individuals with ADHD. 2) To investigate whether other individual- or family-related risk factors for SUD could mediate or confound this association.

DESIGN: Population-based cohort study SETTING AND PARTICIPANTS: ADHD cases in the iPSYCH sample (a Danish case-cohort sample of genotyped cases with specific mental disorders), born in Denmark between 1981 and 2003 (N = 13 116). Register-based information on hospital diagnoses of SUD was available until December 31, 2016.

MEASUREMENTS: We estimated odds ratios (ORs) with 95% confidence intervals (CIs) for any SUD as well as for different SUD types (alcohol, cannabis, and other illicit drugs) and severities (use, abuse, and addiction), with effect sizes corresponding to a comparison of the highest PRS-ADHD decile to the lowest.

FINDINGS: PRS-ADHD were associated with any SUD (OR = 1.30, 95% CI: 1.11-1.51). Estimates were similar across different types and severity levels of SUD. Other risk factors for SUD (male sex, age at ADHD diagnosis, comorbid conduct problems, and parental factors including SUD, mental disorders, and socio-economic status) were independently associated with increased risk of SUD. PRS-ADHD explained a minor proportion of the variance in SUD (0.2% on the liability scale) compared to the other risk factors. The association between PRS-ADHD and any SUD was slightly attenuated (OR = 1.21, 95% CI: 1.03-1.41) after adjusting for the other risk factors for SUD. Furthermore, associations were nominally higher in females than in males (ORfemales = 1.59, 95% CI: 1.19-2.12, ORmales = 1.18, 95% CI: 0.98-1.42).

CONCLUSIONS: A higher genetic liability to attention-deficit/hyperactivity disorder appears to be associated with higher risks of substance use disorders in individuals with attention-deficit/hyperactivity disorder.

Originalsprog	Engelsk
Tidsskrift	Addiction
Vol/bind	115
Udgave nummer	7
Sider (fra-til)	1368-1377
Antal sider	10
ISSN	0965-2140
DOI	https://doi.org/10.1111/add.14910
Status	Udgivet - jul. 2020

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10.1111/add.14910

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Wimberley, T., Agerbo, E., Horsdal, H. T., Ottosen, C., Brikell, I., Als, T. D., Demontis, D., Børglum, A. D., Nordentoft, M., Mors, O., Werge, T., Hougaard, D., Bybjerg-Grauholm, J., Hansen, M. B., Mortensen, P. B., Thapar, A., Riglin, L., Langley, K., & Dalsgaard, S. (2020). Genetic liability to ADHD and substance use disorders in individuals with ADHD. Addiction, 115(7), 1368-1377. https://doi.org/10.1111/add.14910

Wimberley, T, Agerbo, E, Horsdal, HT, Ottosen, C, Brikell, I, Als, TD, Demontis, D, Børglum, AD, Nordentoft, M, Mors, O, Werge, T, Hougaard, D, Bybjerg-Grauholm, J, Hansen, MB, Mortensen, PB, Thapar, A, Riglin, L, Langley, K & Dalsgaard, S 2020, 'Genetic liability to ADHD and substance use disorders in individuals with ADHD', Addiction, bind 115, nr. 7, s. 1368-1377. https://doi.org/10.1111/add.14910

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title = "Genetic liability to ADHD and substance use disorders in individuals with ADHD",

abstract = "AIMS: 1) To investigate whether genetic liability to attention-deficit/hyperactivity disorder (ADHD), indexed by polygenic risk scores for ADHD (PRS-ADHD), is associated with substance use disorders (SUD) in individuals with ADHD. 2) To investigate whether other individual- or family-related risk factors for SUD could mediate or confound this association.DESIGN: Population-based cohort study SETTING AND PARTICIPANTS: ADHD cases in the iPSYCH sample (a Danish case-cohort sample of genotyped cases with specific mental disorders), born in Denmark between 1981 and 2003 (N = 13 116). Register-based information on hospital diagnoses of SUD was available until December 31, 2016.MEASUREMENTS: We estimated odds ratios (ORs) with 95% confidence intervals (CIs) for any SUD as well as for different SUD types (alcohol, cannabis, and other illicit drugs) and severities (use, abuse, and addiction), with effect sizes corresponding to a comparison of the highest PRS-ADHD decile to the lowest.FINDINGS: PRS-ADHD were associated with any SUD (OR = 1.30, 95% CI: 1.11-1.51). Estimates were similar across different types and severity levels of SUD. Other risk factors for SUD (male sex, age at ADHD diagnosis, comorbid conduct problems, and parental factors including SUD, mental disorders, and socio-economic status) were independently associated with increased risk of SUD. PRS-ADHD explained a minor proportion of the variance in SUD (0.2% on the liability scale) compared to the other risk factors. The association between PRS-ADHD and any SUD was slightly attenuated (OR = 1.21, 95% CI: 1.03-1.41) after adjusting for the other risk factors for SUD. Furthermore, associations were nominally higher in females than in males (ORfemales = 1.59, 95% CI: 1.19-2.12, ORmales = 1.18, 95% CI: 0.98-1.42).CONCLUSIONS: A higher genetic liability to attention-deficit/hyperactivity disorder appears to be associated with higher risks of substance use disorders in individuals with attention-deficit/hyperactivity disorder.",

keywords = "Addiction, alcohol, attention-deficit/hyperactivity disorder, cannabis, conduct disorder, family history, polygenic risk, predictors, sex, substance use disorder",

author = "Theresa Wimberley and Esben Agerbo and Horsdal, {Henriette Thisted} and Caecilie Ottosen and Isabell Brikell and Als, {Thomas Damm} and Ditte Demontis and B{\o}rglum, {Anders D} and Merete Nordentoft and Ole Mors and Thomas Werge and David Hougaard and Jonas Bybjerg-Grauholm and Hansen, {Marie Baekvad} and Mortensen, {Preben Bo} and Anita Thapar and Lucy Riglin and Kate Langley and S{\o}ren Dalsgaard",

year = "2020",

month = jul,

doi = "10.1111/add.14910",

language = "English",

volume = "115",

pages = "1368--1377",

journal = "Addiction",

issn = "0965-2140",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "7",

}

TY - JOUR

T1 - Genetic liability to ADHD and substance use disorders in individuals with ADHD

AU - Wimberley, Theresa

AU - Agerbo, Esben

AU - Horsdal, Henriette Thisted

AU - Ottosen, Caecilie

AU - Brikell, Isabell

AU - Als, Thomas Damm

AU - Demontis, Ditte

AU - Børglum, Anders D

AU - Nordentoft, Merete

AU - Mors, Ole

AU - Werge, Thomas

AU - Hougaard, David

AU - Bybjerg-Grauholm, Jonas

AU - Hansen, Marie Baekvad

AU - Mortensen, Preben Bo

AU - Thapar, Anita

AU - Riglin, Lucy

AU - Langley, Kate

AU - Dalsgaard, Søren

PY - 2020/7

Y1 - 2020/7

N2 - AIMS: 1) To investigate whether genetic liability to attention-deficit/hyperactivity disorder (ADHD), indexed by polygenic risk scores for ADHD (PRS-ADHD), is associated with substance use disorders (SUD) in individuals with ADHD. 2) To investigate whether other individual- or family-related risk factors for SUD could mediate or confound this association.DESIGN: Population-based cohort study SETTING AND PARTICIPANTS: ADHD cases in the iPSYCH sample (a Danish case-cohort sample of genotyped cases with specific mental disorders), born in Denmark between 1981 and 2003 (N = 13 116). Register-based information on hospital diagnoses of SUD was available until December 31, 2016.MEASUREMENTS: We estimated odds ratios (ORs) with 95% confidence intervals (CIs) for any SUD as well as for different SUD types (alcohol, cannabis, and other illicit drugs) and severities (use, abuse, and addiction), with effect sizes corresponding to a comparison of the highest PRS-ADHD decile to the lowest.FINDINGS: PRS-ADHD were associated with any SUD (OR = 1.30, 95% CI: 1.11-1.51). Estimates were similar across different types and severity levels of SUD. Other risk factors for SUD (male sex, age at ADHD diagnosis, comorbid conduct problems, and parental factors including SUD, mental disorders, and socio-economic status) were independently associated with increased risk of SUD. PRS-ADHD explained a minor proportion of the variance in SUD (0.2% on the liability scale) compared to the other risk factors. The association between PRS-ADHD and any SUD was slightly attenuated (OR = 1.21, 95% CI: 1.03-1.41) after adjusting for the other risk factors for SUD. Furthermore, associations were nominally higher in females than in males (ORfemales = 1.59, 95% CI: 1.19-2.12, ORmales = 1.18, 95% CI: 0.98-1.42).CONCLUSIONS: A higher genetic liability to attention-deficit/hyperactivity disorder appears to be associated with higher risks of substance use disorders in individuals with attention-deficit/hyperactivity disorder.

AB - AIMS: 1) To investigate whether genetic liability to attention-deficit/hyperactivity disorder (ADHD), indexed by polygenic risk scores for ADHD (PRS-ADHD), is associated with substance use disorders (SUD) in individuals with ADHD. 2) To investigate whether other individual- or family-related risk factors for SUD could mediate or confound this association.DESIGN: Population-based cohort study SETTING AND PARTICIPANTS: ADHD cases in the iPSYCH sample (a Danish case-cohort sample of genotyped cases with specific mental disorders), born in Denmark between 1981 and 2003 (N = 13 116). Register-based information on hospital diagnoses of SUD was available until December 31, 2016.MEASUREMENTS: We estimated odds ratios (ORs) with 95% confidence intervals (CIs) for any SUD as well as for different SUD types (alcohol, cannabis, and other illicit drugs) and severities (use, abuse, and addiction), with effect sizes corresponding to a comparison of the highest PRS-ADHD decile to the lowest.FINDINGS: PRS-ADHD were associated with any SUD (OR = 1.30, 95% CI: 1.11-1.51). Estimates were similar across different types and severity levels of SUD. Other risk factors for SUD (male sex, age at ADHD diagnosis, comorbid conduct problems, and parental factors including SUD, mental disorders, and socio-economic status) were independently associated with increased risk of SUD. PRS-ADHD explained a minor proportion of the variance in SUD (0.2% on the liability scale) compared to the other risk factors. The association between PRS-ADHD and any SUD was slightly attenuated (OR = 1.21, 95% CI: 1.03-1.41) after adjusting for the other risk factors for SUD. Furthermore, associations were nominally higher in females than in males (ORfemales = 1.59, 95% CI: 1.19-2.12, ORmales = 1.18, 95% CI: 0.98-1.42).CONCLUSIONS: A higher genetic liability to attention-deficit/hyperactivity disorder appears to be associated with higher risks of substance use disorders in individuals with attention-deficit/hyperactivity disorder.

KW - Addiction

KW - alcohol

KW - attention-deficit/hyperactivity disorder

KW - cannabis

KW - conduct disorder

KW - family history

KW - polygenic risk

KW - predictors

KW - sex

KW - substance use disorder

UR - http://www.scopus.com/inward/record.url?scp=85078053867&partnerID=8YFLogxK

U2 - 10.1111/add.14910

DO - 10.1111/add.14910

M3 - Journal article

C2 - 31803957

SN - 0965-2140

VL - 115

SP - 1368

EP - 1377

JO - Addiction

JF - Addiction

IS - 7

ER -

Genetic liability to ADHD and substance use disorders in individuals with ADHD

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