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


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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Department of Child and Adolescent Psychiatry
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Biological Psychiatry
Language:English
Date:1 November 2017
Deposited On:03 Apr 2020 08:19
Last Modified:28 Jul 2020 14:19
Publisher:Elsevier
ISSN:0006-3223
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1016/j.biopsych.2016.08.040
PubMed ID:27890468

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