TY  - JOUR
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  - Neuropsychopharmacology
N2  - Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N = 53,293, N = 681,275, and N = 98,697, respectively). We then conducted genome-wide ADHD–BMI and ADHD–obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD–BMI overlapping genes with brain volumes (primary GWAS data N = 10,720–10,928; replication data N = 9428). The dopaminergic gene set was associated with both ADHD (P = 5.81 × 10−3) and BMI (P = 1.63 × 10−5); the circadian rhythm was associated with BMI (P = 1.28 × 10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD–BMI and ADHD–obesity results. The ADHD–BMI overlapping genes were associated with putamen volume (P = 7.7 × 10−3; replication data P = 3.9 × 10−2)—a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD–obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/83570
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-835709
SN  - 1740-634X
VL  - 45
IS  - 7
SP  - 1188
EP  - 1195
PB  - Springer Nature
CY  - London
ER  -