TY  - INPR
A1  - Mota, Nina Roth
A1  - Poelmans, Geert
A1  - Klein, Marieke
A1  - Torrico, Bàrbara
A1  - Fernàndez-Castillo, Noèlia
A1  - Cormand, Bru
A1  - Reif, Andreas
A1  - Franke, Barbara
A1  - Arias Vásquez, Alejandro
T1  - Cross-disorder genetic analyses implicate dopaminergic signaling as a biological link between attention-deficit/hyperactivity disorder and obesity measures
T2  - bioRxiv
N2  - Attention-Deficit/Hyperactivity Disorder (ADHD) is frequently comorbid with other psychiatric disorders and also with somatic conditions, such as obesity. In addition to the clinical overlap, significant genetic correlations have been found between ADHD and obesity as well as body mass index (BMI). The biological mechanisms driving this association are largely unknown, but some candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the link between ADHD and obesity measures. Using the largest GWAS summary statistics currently available for ADHD (N=53,293), BMI (N=681,275), and obesity (N=98,697), we first tested the association of dopaminergic and circadian rhythm gene sets with each phenotype. This hypothesis-driven approach showed that the dopaminergic gene set was associated with both ADHD (P=5.81×10−3) and BMI (P=1.63×10−5), while the circadian rhythm gene set was associated with BMI only (P=1.28×10−3). We then took a data-driven approach by conducting genome-wide ADHD-BMI and ADHD-obesity gene-based meta-analyses, followed by pathway enrichment analyses. This approach further supported the implication of dopaminergic signaling in the link between ADHD and obesity measures, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was significantly enriched in both the ADHD-BMI and ADHD-obesity gene-based meta-analysis results. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering the shared etiological factors underlying the frequently observed ADHD-obesity comorbidity may have important implications in terms of preventive interventions and/or efficient treatment of these conditions.
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/83780
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-837802
UR  - https://www.biorxiv.org/content/10.1101/573808v1
IS  - 573808 Version 1
PB  - bioRxiv
ER  -