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.
Keywords
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Article Info
Publication History
Published online: October 18, 2016
Accepted:
August 8,
2016
Received in revised form:
July 11,
2016
Received:
April 8,
2016
Identification
Copyright
© Society of Biological Psychiatry, 2016.
