Familial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Study

dc.contributor.authorBrikell, Isabell
dc.contributor.authorGhirardi, Laura
dc.contributor.authorD'Onofrio, Brian M.
dc.contributor.authorDunn, David W.
dc.contributor.authorAlmqvist, Catarina
dc.contributor.authorDalsgaard, Søren
dc.contributor.authorKuja-Halkola, Ralf
dc.contributor.authorLarsson, Henrik
dc.contributor.departmentDepartment of Psychiatry, School of Medicineen_US
dc.date.accessioned2017-10-05T17:24:45Z
dc.date.available2017-10-05T17:24:45Z
dc.date.issued2017
dc.description.abstractBackground 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.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationBrikell, I., Ghirardi, L., D’Onofrio, B. M., Dunn, D. W., Almqvist, C., Dalsgaard, S., … Larsson, H. (2017). Familial liability to Epilepsy and ADHD: A Nationwide Cohort Study. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2017.08.006en_US
dc.identifier.urihttps://hdl.handle.net/1805/14247
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.isversionof10.1016/j.biopsych.2017.08.006en_US
dc.relation.journalBiological Psychiatryen_US
dc.rightsPublisher Policyen_US
dc.sourceAuthoren_US
dc.subjectADHDen_US
dc.subjectepilepsyen_US
dc.subjectgeneticsen_US
dc.titleFamilial Liability to Epilepsy and Attention-Deficit/Hyperactivity Disorder: A Nationwide Cohort Studyen_US
dc.typeArticleen_US
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