Familial liability to epilepsy and attention-deficit/hyperactivity disorder: a nationwide cohort study
Open accessAbstract
Background Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence.Methods We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors.Results Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33-3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75-1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54-1.74), full siblings (OR = 1.56, 95% CI = 1.46-1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14-1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96-1.25), and cousins (OR = 1.15, 95% CI = 1.10-1.20). The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23-0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = -0.16-0.79).Conclusions This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders.
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Epilepsy is linked to 2.7-fold and 2.5-fold increased ADHD risk; ADHD linked to fourfold increased epilepsy; epilepsy linked to 3.5-fold higher ADHD likelihood with family risk gradients and genetic/environmental variance components.
“A population-based cohort study of over 900,000 Danish children found that epilepsy was associated with a 2.7-fold increased risk for ADHD (Bertelsen et al., 2016). Another population-based cohort study, of over 12,000 Taiwanese, reported that epilepsy was associated with a 2.5-fold increased risk for ADHD. Conversely, a linked cohort study of over 18,000 Taiwanese found ADHD was associated with a”
From The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder (2021) · cites this paper as Brikell et al., 2018
The Results and Discussion (page unavailable) report an approximately 3.5-fold association between epilepsy and ADHD, risk differences across relatives, and genetic and environmental contributions. The Introduction reports a fourfold epilepsy risk among people with ADHD as a previous finding. This paper does not report the claimed 2.7-fold or 2.5-fold estimates as its own findings; the supplied citing sentence attributes the 2.7-fold estimate to Bertelsen et al. (LLM, conf=0.87)
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- Authors
- Brikell, I., Ghirardi, L., D’Onofrio, B. M., Dunn, D. W., Almqvist, C., Dalsgaard, S., Kuja-Halkola, R., & Larsson, H.
- Affiliations
- Karolinska Institutet (SE)
- Indiana University Health (US)
- Karolinska University Hospital (SE)
- Aarhus University (DK)
- Örebro University (SE)
- Corresponding author
- Brikell, Isabell
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2018-01
- Volume
- 83
- Issue
- 2
- Pages
- 173-180
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC5723535
- OpenAlex
- W2742642703
- Cited by
- 85
- References
- 51
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 15 · 2023: 6 · 2022: 16 · 2021: 13 · 2020: 9 · 2019: 7 · 2018: 5
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biological Psychiatry (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks Open (Indiana University) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institute on Drug Abuse
- American Foundation for Suicide Prevention
- Indiana Clinical and Translational Sciences Institute
- National Science Foundation
- Vetenskapsrådet (2013-2280, 2014-3831)
- National Institute of Mental Health (1R01MH102221)
- U.S. Department of Defense
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- epilepsy, attention deficit hyperactivity disorder, genetic susceptibility, genetic correlation, nonshared environment, shared environment, siblings, comorbidity risk
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Epilepsy, Female, Humans, Male, Registries, Risk Factors, Sweden, Cohort Studies, Genetic Predisposition to Disease, Genetic Association Studies
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