期刊
BIOLOGICAL PSYCHIATRY
卷 82, 期 9, 页码 634-641出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2016.08.040
关键词
Attention-deficit/hyperactivity disorder; bipolar disorder; cross-disorder meta-analysis; genetic correlation; genetic overlap; GWAS
资金
- National Institute of Mental Health (NIMH) [U01 MH094421]
- NIMH [MH081804, MH078151, MH59567, R13MH059126, R01MH094469]
- K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway
- European Community's Seventh Framework Programme [602805, 278948, 602450]
- National Institutes of Health [MH081804, MH078151, MH59567, MH094483]
- Deutsche Forschungsgemeinschaft [KFO 125, TRR 58/B06, Z02, RE1632/5-1, RTG 1256]
- Interdisziplinares Zentrum fur Klinische Forschung (IZKF) [Z-6]
- Netherlands Organization for Scientific Research (NWO) [433-09-229, 016-130-669]
- Netherlands Brain Foundation [15F07[2] 27]
- BBMRI-NL [CP2010-33]
- European Community's Horizon Programme [643051, 667302]
- ECNP for the Research Network
- Merz
- Shire Pharma
- Janssen Cilag
- Medice
- Pfizer
- Ironshore
- Shire
- Akili Interactive Labs
- CogCubed
- Alcobra
- VAYA Pharma
- Neurovance
- Impax
- NeuroLifeSciences
- MRC [G1000708] Funding Source: UKRI
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 (r(Gfull) 5.64, p = 3.13 3 10(-14); r(Grestricted) = .71, p = 4.09 x 10(-16)). The meta-analysis between the full BPD sample identified two genome-wide significant (p(rs7089973) = 2.47 x 10(-8); p(rs11756438) = 4.36 x 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 (p(rs58502974) = 2.11 x 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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