Higher BMI, but not obesity-related genetic polymorphisms, correlates with lower structural connectivity of the reward network in a population-based study

Obesity is of complex origin, involving genetic and neurobehavioral factors. Genetic polymorphisms may increase the risk for developing obesity by modulating dopamine-dependent behaviors, such as reward processing. Yet, few studies have investigated the association of obesity, related genetic varian...

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Vydáno v:International Journal of Obesity Ročník 45; číslo 3; s. 491 - 501
Hlavní autoři: Beyer, Frauke, Zhang, Rui, Scholz, Markus, Wirkner, Kerstin, Loeffler, Markus, Stumvoll, Michael, Villringer, Arno, Witte, A Veronica
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Nature Publishing Group 01.03.2021
Témata:
Adult
Anisotropy
Body Mass Index
Brain - diagnostic imaging
Brain - physiology
Brain - physiopathology
Clustering
Diffusion Magnetic Resonance Imaging
Dopamine
Dopamine D2 receptors
Gene polymorphism
Genetic diversity
Genetic variance
Genetics
Genotyping
Humans
Magnetic resonance imaging
Middle Aged
Neostriatum
Neural networks
Neural Pathways - diagnostic imaging
Neural Pathways - physiology
Neural Pathways - physiopathology
Neuroimaging
Nucleus accumbens
Obesity
Obesity - epidemiology
Obesity - genetics
Obesity - physiopathology
Polymorphism
Polymorphism, Single Nucleotide - genetics
Population studies
Population-based studies
Putamen
Receptors
Reinforcement
Reward
Substantia alba
Young Adult
ISSN:0307-0565, 1476-5497, 1476-5497
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Shrnutí:Obesity is of complex origin, involving genetic and neurobehavioral factors. Genetic polymorphisms may increase the risk for developing obesity by modulating dopamine-dependent behaviors, such as reward processing. Yet, few studies have investigated the association of obesity, related genetic variants, and structural connectivity of the dopaminergic reward network. We analyzed 347 participants (age range: 20-59 years, BMI range: 17-38 kg/m ) of the LIFE-Adult Study. Genotyping for the single nucleotid polymorphisms rs1558902 (FTO) and rs1800497 (near dopamine D2 receptor) was performed on a microarray. Structural connectivity of the reward network was derived from diffusion-weighted magnetic resonance imaging at 3 T using deterministic tractography of Freesurfer-derived regions of interest. Using graph metrics, we extracted summary measures of clustering coefficient and connectivity strength between frontal and striatal brain regions. We used linear models to test the association of BMI, risk alleles of both variants, and reward network connectivity. Higher BMI was significantly associated with lower connectivity strength for number of streamlines (β = -0.0025, 95%-C.I.: [-0.004, -0.0008], p = 0.0042), and, to lesser degree, fractional anisotropy (β = -0.0009, 95%-C.I. [-0.0016, -0.00008], p = 0.031), but not clustering coefficient. Strongest associations were found for left putamen, right accumbens, and right lateral orbitofrontal cortex. As expected, the polymorphism rs1558902 in FTO was associated with higher BMI (F = 6.9, p < 0.001). None of the genetic variants was associated with reward network structural connectivity. Here, we provide evidence that higher BMI correlates with lower reward network structural connectivity. This result is in line with previous findings of obesity-related decline in white matter microstructure. We did not observe an association of variants in FTO or near DRD2 receptor with reward network structural connectivity in this population-based cohort with a wide range of BMI and age. Future research should further investigate the link between genetics, obesity and fronto-striatal structural connectivity.
Bibliografie:ObjectType-Article-1
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ISSN:0307-0565
1476-5497
1476-5497
DOI:10.1038/s41366-020-00702-4