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

van Hulzen, KJE; Scholz, CJ; Franke, B; Ripke, S; Klein, M; McQuillin, A; Sonuga-Barke, EJ; ... Reif, A; + view all (2017) Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis. Biological Psychiatry , 82 (9) pp. 634-641. 10.1016/j.biopsych.2016.08.040. Green open access

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Abstract

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently co-occurring and highly heritable mental health conditions. We hypothesized that BPD cases with an early age of onset (≤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 = .64, p = 3.13 × 10(-14); rGrestricted = .71, p = 4.09 × 10(-16)). The meta-analysis between the full BPD sample identified two genome-wide significant (prs7089973 = 2.47 × 10(-8); prs11756438 = 4.36 × 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 = 2.11 × 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.

Type: Article
Title: Genetic Overlap Between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: Evidence From Genome-wide Association Study Meta-analysis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.biopsych.2016.08.040
Publisher version: https://doi.org/10.1016/j.biopsych.2016.08.040
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Attention-deficit/hyperactivity disorder, GWAS, bipolar disorder, cross-disorder meta-analysis, genetic correlation, genetic overlap
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
URI: https://discovery.ucl.ac.uk/id/eprint/1530687
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