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Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis

van Hulzen, K.J. and Scholz, C.J. and Franke, B. and Ripke, S. and Klein, M. and McQuillin, A. and Sonuga-Barke, E. and PGC ADHD Working Group, and Kelsoe, J.R. and Landen, M. and Andreassen, O.A. and PGC Bipolar Working Group, and Jones, Lisa and Gordon-Smith, Katherine and Lesch, K. and Weber, H. and Faraone, S.V. and Arias-Vasquez, A. and Reif, A. (2016) Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis. Biological Psychiatry. ISSN Online: 0006-3223

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Abstract

ABSTRACT BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently cooccurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age ofonset (#21 years old) would be particularly likely to show genetic covariation with ADHD. METHODS: Genome-wide association study data were available for 4609 individuals with ADHD, 9650 individuals with BPD (5167 thereof with early-onset BPD), and 21,363 typically developing controls. We conducted a cross disorder genome-wide association study meta-analysis to identify whether the observed comorbidity between ADHD and BPD could be due to shared genetic risks. RESULTS: We found a significant single nucleotide polymorphism–based genetic correlation between ADHD and BPD in the full and age-restricted samples (rGfull 5 .64, p 5 3.13 3 10–14; rGrestricted 5 .71, p 5 4.09 3 10–16). The meta-analysis between the full BPD sample identified two genome-wide significant (prs7089973 5 2.47 3 10–8; prs11756438 5 4.36 3 10–8) regions located on chromosomes 6 (CEP85L) and 10 (TAF9BP2). Restricting the analyses to BPD cases with an early onset yielded one genome-wide significant association (prs58502974 5 2.11 3 10–8) on chromosome 5 in the ADCY2 gene. Additional nominally significant regions identified contained known expression quantitative trait loci with putative functional consequences for NT5DC1, NT5DC2, and CACNB3 expression, whereas functional predictions implicated ABLIM1 as an allele-specific expressed gene in neuronal tissue. CONCLUSIONS: The single nucleotide polymorphism–based genetic correlation between ADHD and BPD is substantial, significant, and consistent with the existence of genetic overlap between ADHD and BPD, with potential differential genetic mechanisms involved in early and later BPD onset.

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Uncontrolled Keywords: Attention-deficit/hyperactivity disorder, bipolar disorder, cross-disorder meta-analysis, genetic correlation, genetic overlap, GWAS
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions: Academic Departments > Institute of Health and Society
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Depositing User: Katherine Gordon-Smith
Date Deposited: 20 Jun 2017 08:42
Last Modified: 05 Jul 2017 10:30
URI: https://eprints.worc.ac.uk/id/eprint/5601

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