Association of genetic risk variants with attention-deficit/hyperactivity disorder trajectories in the general population
Open accessAbstract
IMPORTANCE: Attention-deficit/hyperactivity disorder (ADHD) is a heritable neurodevelopmental disorder that shows clinical and genetic overlap with other childhood neurodevelopmental disorders. Levels of ADHD symptoms typically decline across childhood and adolescence, although they remain elevated for some individuals. The determinants of symptom persistence and decline are not yet fully understood. OBJECTIVES: To test the hypothesis that genetic risk variant load for ADHD (indexed by polygenic risk scores [PRS]), but not for other psychiatric disorders, is associated with population-based ADHD symptom trajectories across childhood and adolescence, and to examine whether higher genetic liability for ADHD is correlated with total number of additional neurodevelopmental disorders (multimorbidity) in childhood. DESIGN, SETTING, AND PARTICIPANTS: The Avon Longitudinal Study of Parents and Children, an ongoing prospective population-based cohort study, has been collecting data on 14 701 children, including 9757 with data on symptoms of ADHD at multiple time points, since September 6, 1990. The primary exposure variables, PRS, were generated using results of a genome-wide association study from the Psychiatric Genomics Consortium. Childhood multimorbidity scores (ages 7-9 years) were measured by total impairments in 4 domains known to share genetic liability with ADHD: IQ, social communication, pragmatic language, and conduct. Data analysis was conducted from March 1 to September 8, 2016. MAIN OUTCOMES AND MEASURES: Attention-deficit/hyperactivity disorder symptom trajectories from ages 4 to 17 years (7 time points). RESULTS: Among 9757 children with data on symptoms of ADHD at multiple time points (age range, 4-17 years; 4968 boys and 4789 girls), 4 ADHD symptom trajectories were identified: low (82.6%), intermediate (7.7%), childhood-limited (5.8%), and persistent (3.9%). Mean (SE) PRS for ADHD were higher in children in the persistent trajectory (0.254 [0.069]) compared with each of the other 3 trajectories (low, -0.018 [0.014], χ21 = 14.67, P < .001, odds ratio, 1.31; intermediate, 0.054 [0.055], χ21 = 4.70, P = .03, odds ratio, 1.22; and childhood-limited, 0.017 [0.060], χ21 = 6.50, P = .01, odds ratio, 1.27). Findings were specific to PRS for ADHD; PRS for other psychiatric conditions did not differ across trajectories. The proportion of children with multimorbidity was also highest in those in the persistent trajectory (42.5%; 95% CI, 33.9%-51.1%; P < .001) and was associated with persistence of ADHD symptoms independent of PRS. CONCLUSIONS AND RELEVANCE: Persistence of ADHD symptoms across childhood and adolescence in the general population is associated with higher PRS for ADHD. Childhood multimorbidity was also associated with persistence of ADHD symptoms and may help to identify children with ADHD whose symptoms are most likely to continue into adolescence.
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Polygenic risk scores have been useful for detecting common variant signals in ADHD and other conditions.
“an approach that has proven fruitful in detecting the common variant signal for ADHD28–32 and other disorders.”
From Working Memory and Vigilance as Multivariate Endophenotypes Related to Common Genetic Risk for Attention-Deficit/Hyperactivity Disorder (2018) · cites this paper as [30]
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- Authors
- Riglin, L., Collishaw, S., Thapar, A. K., Dalsgaard, S., Langley, K., Smith, G. D., Stergiakouli, E., Maughan, B., O’Donovan, M. C., & Thapar, A.
- Affiliations
- Cardiff University (GB)
- Aarhus University (DK)
- University of Bristol (GB)
- King's College London (GB)
- Corresponding author
- Thapar, Anita
- ORCID
- Venue
- JAMA Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2016-12-01
- Volume
- 73
- Issue
- 12
- Pages
- 1285
- ISSN
- 2168-622X (ISSN-L)
- PMC
- PMC6485350
- OpenAlex
- W2549024283
- Cited by
- 161
- References
- 59
- Citations by year
- 2026: 16 · 2025: 15 · 2024: 11 · 2023: 13 · 2022: 25 · 2021: 17 · 2020: 17 · 2019: 23 · 2018: 12 · 2017: 9 · 2016: 2 · 2012: 1
- FWCI
- 13.63
- Type
- journal article
- Language
- en
- Open access
- green
- kclpure.kcl.ac.uk
- Licence
- other-oa
- Locations
- JAMA Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Bristol Research (University of Bristol) (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Explore Bristol Research (acceptedVersion, other-oa)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- Wellcome Trust (102215/2/13/2), 102215)
- University of Bristol (MC_UU_12013/1, 102215/2/13/2)
- Lundbeckfonden (R155-2014-1724)
- Medical Research Council (102215, MC_UU_12013, MR/M012964/1, MCUU12013/1, 102215/2/13/2, MR/L010305/1, MC_PC_15018)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- attention deficit hyperactivity disorder, polygenic risk score, genetic susceptibility, symptom trajectories, persistent ADHD, multimorbidity, neurodevelopmental disorders, IQ, social communication, pragmatic language, conduct problems, Avon Longitudinal Study of Parents and Children, heritability, childhood and adolescence, psychiatric comorbidity, genetic risk variants, genome-wide association study
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, England, Female, Genetics, Population, Humans, Longitudinal Studies, Male, Population Surveillance, Genetic Variation, Cohort Studies, Comorbidity, Case-Control Studies, Conduct Disorder, Genetic Predisposition to Disease, Multifactorial Inheritance, Genetic Load, Neurodevelopmental Disorders
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