Interplay of ADHD Polygenic Liability With Birth-Related, Somatic, and Psychosocial Factors in ADHD: A Nationwide Study

Isabell Brikell; Theresa Wimberley; Clara Albiñana; Bjarni Jóhann Vilhjálmsson; Esben Agerbo; Anders D Børglum; Ditte Demontis; Andrew J Schork; Sonja LaBianca; Thomas Werge; David M Hougaard; Merete Nordentoft; Ole Mors; Preben Bo Mortensen; Liselotte Vogdrup Petersen; Søren Dalsgaard

doi:10.1176/appi.ajp.21111105

Interplay of ADHD Polygenic Liability With Birth-Related, Somatic, and Psychosocial Factors in ADHD: A Nationwide Study

Isabell Brikell, Theresa Wimberley, Clara Albiñana, Bjarni Jóhann Vilhjálmsson, Esben Agerbo, Anders D Børglum, Ditte Demontis, Andrew J Schork, Sonja LaBianca, Thomas Werge, David M Hougaard, Merete Nordentoft, Ole Mors, Preben Bo Mortensen, Liselotte Vogdrup Petersen, Søren Dalsgaard

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

6 Citations (Scopus)

Abstract

Objective: Attention deficit hyperactivity disorder (ADHD) is a Results: ADHD PRS was associated with 12 of 24 risk factors multifactorial neurodevelopmental disorder, yet the interplay (odds ratio range, 1.03–1.30), namely, small gestational age, between ADHD polygenic risk scores (PRSs) and other risk infections, traumatic brain injury, and most psychosocial risk factors remains relatively unexplored. The authors investifactors. Nineteen risk factors were associated with ADHD digated associations, confounding, and interactions of ADHD agnosis (odds ratio range, 1.20–3.68), and adjusting for ADHD PRS with birth-related, somatic, and psychosocial factors PRS and parental psychiatric history led to only minor attenpreviously associated with ADHD. uations. Only the interaction between ADHD PRS and maternal autoimmune disease survived correction for multiple testing. Methods: Participants included a random general population sample (N521,578) and individuals diagnosed with ADHD Conclusions: Higher ADHD PRS in the general population is (N513,697) from the genotyped Danish iPSYCH2012 case associated with small increases in risk for certain birth-related cohort, born between 1981 and 2005. The authors derived and somatic ADHD risk factors, and broadly to psychosocial ADHD PRSs and identified 24 factors previously associated adversity. Evidence of gene-environment interaction was with ADHD using national registers. Logistic regression was limited, as was confounding by ADHD PRS and family psyused to estimate associations of ADHD PRS with each risk chiatric history on ADHD risk factor associations. This suggests factor in the general population. Cox models were used to that the majority of the investigated ADHD risk factors act largely evaluate confounding of risk factor associations with ADHD independently of current ADHD PRS to increase risk of ADHD. diagnosis by ADHD PRS and parental psychiatric history, and interactions between ADHD PRS and each risk factor. Am J Psychiatry 2023; 180:73–88; doi: 10.1176/appi.ajp.21111105

Original language	English
Journal	The American Journal of Psychiatry (Spanish Edition)
Volume	180
Issue	1
Pages (from-to)	73-88
Number of pages	16
ISSN	1139-3475
DOIs	https://doi.org/10.1176/appi.ajp.21111105
Publication status	Published - Jan 2023

Keywords

Attention Deficit Hyperactivity Disorder (ADHD)
Environmental Risk Factors
Genetics/Genomics
Neurodevelopmental Disorders

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10.1176/appi.ajp.21111105

https://www.medrxiv.org/content/medrxiv/early/2021/08/24/2021.08.18.21262211.full.pdfLicence: CC BY-NC-ND

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Brikell, I., Wimberley, T., Albiñana, C., Vilhjálmsson, B. J., Agerbo, E., Børglum, A. D., Demontis, D., Schork, A. J., LaBianca, S., Werge, T., Hougaard, D. M., Nordentoft, M., Mors, O., Mortensen, P. B., Petersen, L. V., & Dalsgaard, S. (2023). Interplay of ADHD Polygenic Liability With Birth-Related, Somatic, and Psychosocial Factors in ADHD: A Nationwide Study. The American Journal of Psychiatry (Spanish Edition), 180(1), 73-88. https://doi.org/10.1176/appi.ajp.21111105

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title = "Interplay of ADHD Polygenic Liability With Birth-Related, Somatic, and Psychosocial Factors in ADHD: A Nationwide Study",

abstract = "Objective: Attention deficit hyperactivity disorder (ADHD) is a Results: ADHD PRS was associated with 12 of 24 risk factors multifactorial neurodevelopmental disorder, yet the interplay (odds ratio range, 1.03–1.30), namely, small gestational age, between ADHD polygenic risk scores (PRSs) and other risk infections, traumatic brain injury, and most psychosocial risk factors remains relatively unexplored. The authors investifactors. Nineteen risk factors were associated with ADHD digated associations, confounding, and interactions of ADHD agnosis (odds ratio range, 1.20–3.68), and adjusting for ADHD PRS with birth-related, somatic, and psychosocial factors PRS and parental psychiatric history led to only minor attenpreviously associated with ADHD. uations. Only the interaction between ADHD PRS and maternal autoimmune disease survived correction for multiple testing. Methods: Participants included a random general population sample (N521,578) and individuals diagnosed with ADHD Conclusions: Higher ADHD PRS in the general population is (N513,697) from the genotyped Danish iPSYCH2012 case associated with small increases in risk for certain birth-related cohort, born between 1981 and 2005. The authors derived and somatic ADHD risk factors, and broadly to psychosocial ADHD PRSs and identified 24 factors previously associated adversity. Evidence of gene-environment interaction was with ADHD using national registers. Logistic regression was limited, as was confounding by ADHD PRS and family psyused to estimate associations of ADHD PRS with each risk chiatric history on ADHD risk factor associations. This suggests factor in the general population. Cox models were used to that the majority of the investigated ADHD risk factors act largely evaluate confounding of risk factor associations with ADHD independently of current ADHD PRS to increase risk of ADHD. diagnosis by ADHD PRS and parental psychiatric history, and interactions between ADHD PRS and each risk factor. Am J Psychiatry 2023; 180:73–88; doi: 10.1176/appi.ajp.21111105",

keywords = "Attention Deficit Hyperactivity Disorder (ADHD), Environmental Risk Factors, Genetics/Genomics, Neurodevelopmental Disorders",

author = "Isabell Brikell and Theresa Wimberley and Clara Albi{\~n}ana and Vilhj{\'a}lmsson, {Bjarni J{\'o}hann} and Esben Agerbo and B{\o}rglum, {Anders D} and Ditte Demontis and Schork, {Andrew J} and Sonja LaBianca and Thomas Werge and Hougaard, {David M} and Merete Nordentoft and Ole Mors and Mortensen, {Preben Bo} and Petersen, {Liselotte Vogdrup} and S{\o}ren Dalsgaard",

year = "2023",

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doi = "10.1176/appi.ajp.21111105",

language = "English",

volume = "180",

pages = "73--88",

journal = "The American Journal of Psychiatry (Spanish Edition)",

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number = "1",

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Brikell, I , Wimberley, T , Albiñana, C , Vilhjálmsson, BJ , Agerbo, E , Børglum, AD , Demontis, D, Schork, AJ, LaBianca, S, Werge, T, Hougaard, DM, Nordentoft, M, Mors, O , Mortensen, PB , Petersen, LV & Dalsgaard, S 2023, 'Interplay of ADHD Polygenic Liability With Birth-Related, Somatic, and Psychosocial Factors in ADHD: A Nationwide Study', The American Journal of Psychiatry (Spanish Edition), vol. 180, no. 1, pp. 73-88. https://doi.org/10.1176/appi.ajp.21111105

Interplay of ADHD Polygenic Liability With Birth-Related, Somatic, and Psychosocial Factors in ADHD: A Nationwide Study. / Brikell, Isabell ; Wimberley, Theresa ; Albiñana, Clara et al.
In: The American Journal of Psychiatry (Spanish Edition), Vol. 180, No. 1, 01.2023, p. 73-88.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Interplay of ADHD Polygenic Liability With Birth-Related, Somatic, and Psychosocial Factors in ADHD

T2 - A Nationwide Study

AU - Brikell, Isabell

AU - Wimberley, Theresa

AU - Albiñana, Clara

AU - Vilhjálmsson, Bjarni Jóhann

AU - Agerbo, Esben

AU - Børglum, Anders D

AU - Demontis, Ditte

AU - Schork, Andrew J

AU - LaBianca, Sonja

AU - Werge, Thomas

AU - Hougaard, David M

AU - Nordentoft, Merete

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Petersen, Liselotte Vogdrup

AU - Dalsgaard, Søren

PY - 2023/1

Y1 - 2023/1

N2 - Objective: Attention deficit hyperactivity disorder (ADHD) is a Results: ADHD PRS was associated with 12 of 24 risk factors multifactorial neurodevelopmental disorder, yet the interplay (odds ratio range, 1.03–1.30), namely, small gestational age, between ADHD polygenic risk scores (PRSs) and other risk infections, traumatic brain injury, and most psychosocial risk factors remains relatively unexplored. The authors investifactors. Nineteen risk factors were associated with ADHD digated associations, confounding, and interactions of ADHD agnosis (odds ratio range, 1.20–3.68), and adjusting for ADHD PRS with birth-related, somatic, and psychosocial factors PRS and parental psychiatric history led to only minor attenpreviously associated with ADHD. uations. Only the interaction between ADHD PRS and maternal autoimmune disease survived correction for multiple testing. Methods: Participants included a random general population sample (N521,578) and individuals diagnosed with ADHD Conclusions: Higher ADHD PRS in the general population is (N513,697) from the genotyped Danish iPSYCH2012 case associated with small increases in risk for certain birth-related cohort, born between 1981 and 2005. The authors derived and somatic ADHD risk factors, and broadly to psychosocial ADHD PRSs and identified 24 factors previously associated adversity. Evidence of gene-environment interaction was with ADHD using national registers. Logistic regression was limited, as was confounding by ADHD PRS and family psyused to estimate associations of ADHD PRS with each risk chiatric history on ADHD risk factor associations. This suggests factor in the general population. Cox models were used to that the majority of the investigated ADHD risk factors act largely evaluate confounding of risk factor associations with ADHD independently of current ADHD PRS to increase risk of ADHD. diagnosis by ADHD PRS and parental psychiatric history, and interactions between ADHD PRS and each risk factor. Am J Psychiatry 2023; 180:73–88; doi: 10.1176/appi.ajp.21111105

AB - Objective: Attention deficit hyperactivity disorder (ADHD) is a Results: ADHD PRS was associated with 12 of 24 risk factors multifactorial neurodevelopmental disorder, yet the interplay (odds ratio range, 1.03–1.30), namely, small gestational age, between ADHD polygenic risk scores (PRSs) and other risk infections, traumatic brain injury, and most psychosocial risk factors remains relatively unexplored. The authors investifactors. Nineteen risk factors were associated with ADHD digated associations, confounding, and interactions of ADHD agnosis (odds ratio range, 1.20–3.68), and adjusting for ADHD PRS with birth-related, somatic, and psychosocial factors PRS and parental psychiatric history led to only minor attenpreviously associated with ADHD. uations. Only the interaction between ADHD PRS and maternal autoimmune disease survived correction for multiple testing. Methods: Participants included a random general population sample (N521,578) and individuals diagnosed with ADHD Conclusions: Higher ADHD PRS in the general population is (N513,697) from the genotyped Danish iPSYCH2012 case associated with small increases in risk for certain birth-related cohort, born between 1981 and 2005. The authors derived and somatic ADHD risk factors, and broadly to psychosocial ADHD PRSs and identified 24 factors previously associated adversity. Evidence of gene-environment interaction was with ADHD using national registers. Logistic regression was limited, as was confounding by ADHD PRS and family psyused to estimate associations of ADHD PRS with each risk chiatric history on ADHD risk factor associations. This suggests factor in the general population. Cox models were used to that the majority of the investigated ADHD risk factors act largely evaluate confounding of risk factor associations with ADHD independently of current ADHD PRS to increase risk of ADHD. diagnosis by ADHD PRS and parental psychiatric history, and interactions between ADHD PRS and each risk factor. Am J Psychiatry 2023; 180:73–88; doi: 10.1176/appi.ajp.21111105

KW - Attention Deficit Hyperactivity Disorder (ADHD)

KW - Environmental Risk Factors

KW - Genetics/Genomics

KW - Neurodevelopmental Disorders

U2 - 10.1176/appi.ajp.21111105

DO - 10.1176/appi.ajp.21111105

M3 - Journal article

C2 - 36069019

SN - 1139-3475

VL - 180

SP - 73

EP - 88

JO - The American Journal of Psychiatry (Spanish Edition)

JF - The American Journal of Psychiatry (Spanish Edition)

IS - 1

ER -

Interplay of ADHD Polygenic Liability With Birth-Related, Somatic, and Psychosocial Factors in ADHD: A Nationwide Study

Abstract

Keywords

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