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Genetic overlap between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: evidence from GWAS meta-analysis

Genetic overlap between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: evidence from GWAS meta-analysis
Genetic overlap between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: evidence from GWAS meta-analysis
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.
0006-3223
1-17
van Hulzen, K.J.E.
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Scholz, C.J.
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Franke, B.
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Ripke, S.
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Klein, M.
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McQuillin, A.
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Sonuga-Barke, E.J.
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Kelsoe, J.R.
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Landen, M.
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Andreassen, O.A.
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Lesch, K.-P.
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Weber, H.
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Faraone, S.V.
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Arias-Vasquez, A.
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Reif, A.
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van Hulzen, K.J.E.
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Scholz, C.J.
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Franke, B.
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Ripke, S.
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Klein, M.
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McQuillin, A.
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Sonuga-Barke, E.J.
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Kelsoe, J.R.
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Landen, M.
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Andreassen, O.A.
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Lesch, K.-P.
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Weber, H.
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Faraone, S.V.
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Arias-Vasquez, A.
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Reif, A.
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van Hulzen, K.J.E., Scholz, C.J., Franke, B., Ripke, S., Klein, M., McQuillin, A., Sonuga-Barke, E.J., Kelsoe, J.R., Landen, M., Andreassen, O.A., Lesch, K.-P., Weber, H., Faraone, S.V., Arias-Vasquez, A. and Reif, A. (2016) Genetic overlap between Attention-Deficit/Hyperactivity Disorder and Bipolar Disorder: evidence from GWAS meta-analysis. Biological Psychiatry, 1-17. (doi:10.1016/j.biopsych.2016.08.040). (PMID:27890468)

Record type: Article

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.

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More information

Accepted/In Press date: 8 August 2016
e-pub ahead of print date: 18 October 2016
Additional Information: PGC ADHD Working Group, PGC Bipolar Working Group
Organisations: Clinical Neuroscience

Identifiers

Local EPrints ID: 399606
URI: https://eprints.soton.ac.uk/id/eprint/399606
ISSN: 0006-3223
PURE UUID: ad2da6b3-19ef-4e92-8846-25432b73bad0

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Date deposited: 22 Aug 2016 10:21
Last modified: 10 Jan 2018 05:16

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Contributors

Author: K.J.E. van Hulzen
Author: C.J. Scholz
Author: B. Franke
Author: S. Ripke
Author: M. Klein
Author: A. McQuillin
Author: E.J. Sonuga-Barke
Author: J.R. Kelsoe
Author: M. Landen
Author: O.A. Andreassen
Author: K.-P. Lesch
Author: H. Weber
Author: S.V. Faraone
Author: A. Arias-Vasquez
Author: A. Reif

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