Neurobehavioural Correlates of Obesity are Largely Heritable

Abstract

Recent molecular genetic studies have shown that the majority of genes associated with obesity are expressed in the central nervous system. Obesity has also been associated with neurobehavioural factors such as brain morphology, cognitive performance, and personality.Here, we tested whether these neurobehavioural factors were associated with the heritable variance in obesity measured by body mass index (BMI) in the Human Connectome Project (N=895 siblings). Phenotypically, cortical thickness findings supported the "right brain hypothesis" for obesity. Namely, increased BMI associated with decreased cortical thickness in right frontal lobe and increased thickness in the left frontal lobe, notably in lateral prefrontal cortex. In addition, lower thickness and volume in entorhinal-parahippocampal structures, and increased thickness in parietal-occipital structures in participants with higher BMI supported the role of visuospatial function in obesity. Brain morphometry results were supported by cognitive tests, which outlined a negative association between BMI and visuospatial function, verbal episodic memory, impulsivity, and cognitive flexibility. Personality-BMI correlations were inconsistent. We then aggregated the effects for each neurobehavioural factor for a behavioural genetics analysis and estimated each factor's genetic overlap with BMI. Cognitive test scores and brain morphometry had 0.25 -0.45 genetic correlations with BMI, and the phenotypic correlations with BMI were 77-89% explained by genetic factors. Neurobehavioural factors also had some genetic overlap with each other. In summary, obesity as measured by BMI has considerable genetic overlap with brain and cognitive measures. This supports the theory that obesity is inherited via brain function, and may inform intervention strategies. Significance StatementObesity is a widespread heritable health condition. Evidence from psychology, cognitive neuroscience, and genetics has proposed links between obesity and the brain. The current study tested whether the heritable variance in body mass index (BMI) is explained by brain and behavioural factors in a large brain imaging cohort that included multiple related individuals. We found that the heritable variance in BMI had genetic correlations 0.25 -0.45 with cognitive tests, cortical thickness, and regional brain volume. In particular, BMI was associated with frontal lobe asymmetry and differences in temporal-parietal perceptual systems. Further, we found genetic overlap between certain brain and behavioural factors. In summary, the genetic vulnerability to BMI is expressed in the brain. This may inform intervention strategies. \body

Association between regional brain volumes and BMI z-score change over one year in children

“…We did not find evidence to support the hypotheses that entorhinal cortex volume was cross-sectionally associated with BMIz in children, however, we did find that entorhinal cortex volume was negatively associated with changes in BMIz longitudinally. Therefore, while our findings do not support cross-sectional results like those found in adults[4] it does suggest a negative longitudinal relationship between entorhinal cortex volume and increases in BMIz over a one-year period within this small sample. The lack of replication of the cross-sectional relationship between entorhinal volume and BMIz may be in part due to the limited number of children with overweight or obesity in our sample or our sample’s younger age range.…”

“…However, contrary to our initial hypothesis we did observe a positive association between concurrent right hippocampal volume and BMIz at timepoint 2 in both cross-sectional and SEM results. Our cross-sectional findings add support to those previously reported in adolescents [6] however, we note that there are conflicting results in the current literature with some studies showing no relationship [3,4] and others observing the opposite relationship to that observed in this study [16,25,43]. The lack of a relationship with BMIz at baseline may suggest that BMIz-related associations with this region do not emerge until later in development.…”

Searching for the causal effects of BMI in over 300 000 individuals, using Mendelian randomization

“…Several previous observational studies have reported the association of anxiety and BMI. The prevalence of anxiety has been shown to be higher in obese compared with non-obese people 43–47 , although Vainik et al found no correlation between BMI and neuroticism 48 . The few instrumental variable studies estimating the causal effect of BMI on anxiety that have been performed to date (one specifically looking at phobic anxiety 49 and the other using an anxiety measure defined using the Hospital Anxiety and Depression Scale (HADS) 50 ), did not find evidence of a causal effect, although this may be due to insufficient statistical power 49,50 .…”

Investigating the genetic and environmental basis of head micromovements during MRI

“…Higher head motion has been consistently reported in attention-deficit disorder (ADHD) and is phenotypically and genetically correlated with impulsivity (Couvy-Duchesne et al, 2016;Kong et al, 2014;Thomson et al, 2020). Impulsivity and decreased inhibitory control show small yet reliable association with BMI, which could be in part explained by shared genetic factors (Meule & Blechert, 2016;Vainik et al, 2018). Head motion is moderately heritable (h² ~ 0.4) and shares genetic variance with BMI (ρg ~ 0.8) in studies based on family structure (Couvy-Duchesne et al, 2014;Engelhardt et al, 2017;Hodgson et al, 2016).…”