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Preliminary evidence for genetic overlap between body mass index and striatal reward response

Lancaster, Thomas, Ihssen, I., Brindley, L.M. and Linden, David 2018. Preliminary evidence for genetic overlap between body mass index and striatal reward response. Translational Psychiatry 8 , 19. 10.1038/s41398-017-0068-4

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Abstract

The reward-processing network is implicated in the aetiology of obesity. Several lines of evidence suggest obesitylinked genetic risk loci (such as DRD2 and FTO) may influence individual variation in body mass index (BMI) through neuropsychological processes reflected in alterations in activation of the striatum during reward processing. However, no study has tested the broader hypotheses that (a) the relationship between BMI and reward-related brain activation (measured through the blood oxygenation-dependent (BOLD) signal) may be observed in a large population study and (b) the overall genetic architecture of these phenotypes overlap, an assumption critical for the progression of imaging genetic studies in obesity research. Using data from the Human Connectome Project (N = 1055 healthy, young individuals: average BMI = 26.4), we first establish a phenotypic relationship between BMI and ventral striatal (VS) BOLD during the processing of rewarding (monetary) stimuli (β = 0.44, P = 0.013), accounting for potential confounds. BMI and VS BOLD were both significantly influenced by additive genetic factors (H2r = 0.57; 0.12, respectively). Further decomposition of this variance suggested that the relationship was driven by shared genetic (ρg = 0.47, P = 0.011), but not environmental (ρE = −0.07, P = 0.29) factors. To validate the assumption of genetic pleiotropy between BMI and VS BOLD, we further show that polygenic risk for higher BMI is also associated with increased VS BOLD response to appetitive stimuli (calorically high food images), in an independent sample (N = 81; PFWE−ROI o 0.005). Together, these observations suggest that the genetic factors link risk to obesity to alterations within key nodes of the brain's reward circuity. These observations provide a basis for future work exploring the mechanistic role of genetic loci that confer risk for obesity using the imaging genetics approach.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Cardiff University Brain Research Imaging Centre (CUBRIC)
Medicine
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Psychology
Publisher: Nature Publishing Group
ISSN: 2158-3188
Funders: Medical Research Council
Date of First Compliant Deposit: 31 January 2018
Date of Acceptance: 26 October 2017
Last Modified: 14 Feb 2019 12:25
URI: http://orca-mwe.cf.ac.uk/id/eprint/108660

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