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

Beyer, F., Zhang, R., Scholz, M., Wirkner, K., Loeffler, M., Stumvoll, M., et al. (2020). Higher BMI, but not obesity-related genetic polymorphisms, correlates with lower structural connectivity of the reward network in a population-based study. International Journal of Obesity. doi:10.1038/s41366-020-00702-4.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-678E-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-678F-5
Genre: Journal Article

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 Creators:
Beyer, Frauke1, 2, Author              
Zhang, Rui1, Author              
Scholz, Markus3, 4, Author
Wirkner, Kerstin4, Author
Loeffler, Markus3, 4, Author
Stumvoll, Michael2, 5, Author
Villringer, Arno1, 2, 6, Author              
Witte, A. Veronica1, 2, Author              
Affiliations:
1Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
2Collaborative Research Center Obesity Mechanisms, Institute of Biochemistry, University of Leipzig, Germany, ou_persistent22              
3Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Germany, ou_persistent22              
4Leipzig Research Center for Civilization Diseases (LIFE), University of Leipzig, Germany, ou_persistent22              
5Clinic for Endocrinology and Nephrology, University Hospital Leipzig, Germany, ou_persistent22              
6Clinic for Cognitive Neurology, University of Leipzig, Germany, ou_persistent22              

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Free keywords: Epidemiology; Neuroscience
 Abstract: Background: 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. Methods: We analyzed 347 participants (age range: 20-59 years, BMI range: 17-38 kg/m2) 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. Results: 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. Conclusions: 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.

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Language(s): eng - English
 Dates: 2020-09-132020-05-052020-10-142020-10-25
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s41366-020-00702-4
Other: online ahead of print
PMID: 33100325
 Degree: -

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Project name : -
Grant ID : CRC 1052
Funding program : -
Funding organization : German Research Foundation

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Title: International Journal of Obesity
  Other : Int. J. Obes.
Source Genre: Journal
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Affiliations:
Publ. Info: Hampshire, UK : Macmillan Press
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 0307-0565
CoNE: https://pure.mpg.de/cone/journals/resource/954925515513_1