Shared genetic variance between obesity and white matter integrity in Mexican Americans

Spieker, Elena A.; Kochunov, Peter; Rowland, Laura M.; Sprooten, Emma; Winkler, Anderson M.; Olvera, Rene L.; Almasy, Laura; Duggirala, Ravindranath; Fox, Peter T.; Blangero, John; Glahn, David C.; Curran, Joanne E.

doi:10.3389/fgene.2015.00026

Cited by 16 publications

(24 citation statements)

References 66 publications

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“…BMI is often associated with reduced white matter microstructure (Ryan et al, 2017;Spieker et al, 2015;Stanek et al, 2011) and higher circulating levels of IL-6, IL-8, and TNFα (Bruun, Pedersen, Kristensen, & Richelsen, 2002;Bruun, Verdich, Toubro, Astrup, & Richelsen, 2003;Straczkowski et al, 2002), making it an important factor to consider in genetic correlation models. Indeed, in our sample BMI was phenotypically correlated with IL-6, TNFα, and a few white matter tracts and genetically correlated with IL-6.…”

Section: Discussionmentioning

confidence: 99%

Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

Rodrigue

Knowles

Mollon

et al. 2019

Human Brain Mapping

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White matter microstructure is affected by immune system activity via the actions of circulating pro‐inflammatory cytokines. Although white matter microstructure and inflammatory measures are significantly heritable, it is unclear if overlapping genetic factors influence these traits in humans. We conducted genetic correlation analyses of these traits using randomly ascertained extended pedigrees from the Genetics of Brain Structure and Function Study (N = 1862, 59% females, ages 18–97 years; 42 ± 15.7). White matter microstructure was assessed using fractional anisotropy (FA) calculated from diffusion tensor imaging (DTI). Circulating levels (pg/mL) of pro‐inflammatory cytokines (IL‐6, IL‐8, and TNFα) phenotypically associated with white matter microstructure were quantified from blood serum. All traits were significantly heritable (h2 ranging from 0.41 to 0.66 for DTI measures and from 0.18 to 0.30 for inflammatory markers). Phenotypically, higher levels of circulating inflammatory markers were associated with lower FA values across the brain (r = −.03 to r = −.17). There were significant negative genetic correlations between most DTI measures and IL‐8 and TNFα, although effects for TNFα were no longer significant when covarying for body mass index. Genetic correlations between DTI measures and IL‐6 were not significant. Understanding the genetic correlation between specific inflammatory markers and DTI measures may help researchers focus questions related to inflammatory processes and brain structure.

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Section: Discussionmentioning

confidence: 99%

Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

Rodrigue

Knowles

Mollon

et al. 2019

Human Brain Mapping

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“…In previous research, these traits have shown high heritability and significant genetic correlation with measures of brain integrity (Glahn et al, ; Kochunov et al, , ). We also considered body mass index (BMI) and systolic and diastolic blood pressures based on research linking body adiposity to cerebral integrity (Kochunov, Glahn, Lancaster, et al, ; Ryan et al, ; Spieker et al, ).…”

Section: Introductionmentioning

confidence: 99%

Genomic kinship construction to enhance genetic analyses in the human connectome project data

Kochunov

Donohue

Mitchell

et al. 2018

Human Brain Mapping

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Imaging genetic analyses quantify genetic control over quantitative measurements of brain structure and function using coefficients of relationship (CR) that code the degree of shared genetics between subjects. CR can be inferred through self-reported relatedness or calculated empirically using genome-wide SNP scans. We hypothesized that empirical CR provides a more accurate assessment of shared genetics than self-reported relatedness. We tested this in 1,046 participants of the Human Connectome Project (HCP) (480 M/566 F) recruited from the Missouri twin registry.We calculated the heritability for 17 quantitative traits drawn from four categories (brain diffusion and structure, cognition, and body physiology) documented by the HCP. We compared the heritability and genetic correlation estimates calculated using self-reported and empirical CR methods Kinship-based INference for GWAS (KING) and weighted allelic correlation (WAC). The polygenetic nature of traits was assessed by calculating the empirical CR from chromosomal SNP sets. The heritability estimates based on whole-genome empirical CR were higher but remained significantly correlated (r $0.9) with those obtained using self-reported values. Population stratification in the HCP sample has likely influenced the empirical CR calculations and biased heritability estimates.Heritability values calculated using empirical CR for chromosomal SNP sets were significantly correlated with the chromosomal length (r 0.7) suggesting a polygenic nature for these traits. The Peter Kochunov and Brian Donohue have contributed equally to this work.

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“…The main goal was to assess whether the aforementioned obesity-neurobehavioural associations are of genetic or environmental origin. Recent evidence from behavioural and molecular genetics suggests that there is considerable genetic overlap between obesity, cognitive test scores, and brain imaging findings (15)(16)(17)(18)(19)(20). However, the evidence so far is not comprehensive across all neurobehavioural factors discussed.…”

Section: Introductionmentioning

confidence: 99%

Neurobehavioural Correlates of Obesity are Largely Heritable

Vainik

Baker

Alanis

et al. 2017

Preprint

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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

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Shared genetic variance between obesity and white matter integrity in Mexican Americans

Cited by 16 publications

References 66 publications

Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

Evidence for genetic correlation between human cerebral white matter microstructure and inflammation

Genomic kinship construction to enhance genetic analyses in the human connectome project data

Neurobehavioural Correlates of Obesity are Largely Heritable

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