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

Artikel i vetenskaplig tidskrift
Författare Kimm J E van Hulzen
Claus J Scholz
Barbara Franke
Stephan Ripke
Marieke Klein
Andrew McQuillin
Edmund J Sonuga-Barke
John R Kelsoe
Mikael Landén
Ole A Andreassen
Klaus-Peter Lesch
Heike Weber
Stephen V Faraone
Alejandro Arias-Vasquez
Andreas Reif
Publicerad i Biological psychiatry
Volym 82
Nummer/häfte 9
Sidor 634-641
ISSN 1873-2402
Publiceringsår 2017
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 634-641
Språk en
Länkar dx.doi.org/10.1016/j.biopsych.2016....
www.ncbi.nlm.nih.gov/entrez/query.f...
Ämneskategorier Psykiatri

Sammanfattning

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.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.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.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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