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. 2024 Jan;32(1):156-165.
doi: 10.1002/oby.23926. Epub 2023 Oct 10.

FTO variation and early frontostriatal brain development in children

Gita Thapaliya  1 , Poorbita Kundu  2 , Elena Jansen  1 , Marcus A Naymik  3 , Richard Lee  4 , Muriel Marisa Katharina Bruchhage  5   6   7 , Viren D'Sa  6 , Matthew J Huentelman  3 , Candace R Lewis  3   8 , Hans-Georg Müller  2 , Sean C L Deoni  9 ; RESONANCE consortium; Susan Carnell  1
Affiliations

FTO variation and early frontostriatal brain development in children

Gita Thapaliya et al. Obesity (Silver Spring). 2024 Jan.

Abstract

Objective: Common obesity-associated genetic variants at the fat mass and obesity-associated (FTO) locus have been associated with appetitive behaviors and altered structure and function of frontostriatal brain regions. The authors aimed to investigate the influence of FTO variation on frontostriatal appetite circuits in early life.

Methods: Data were drawn from RESONANCE, a longitudinal study of early brain development. Growth trajectories of nucleus accumbens and frontal lobe volumes, as well as total gray matter and white matter volume, by risk allele (AA) carrier status on FTO single-nucleotide polymorphism rs9939609 were examined in 228 children (102 female, 126 male) using magnetic resonance imaging assessments obtained from infancy through middle childhood. The authors fit functional concurrent regression models with brain volume outcomes over age as functional responses, and FTO genotype, sex, BMI z score, and maternal education were included as predictors.

Results: Bootstrap pointwise 95% CI for regression coefficient functions in the functional concurrent regression models showed that the AA group versus the group with no risk allele (TT) had greater nucleus accumbens volume (adjusted for total brain volume) in the interval of 750 to 2250 days (2-6 years).

Conclusions: These findings suggest that common genetic risk for obesity is associated with differences in early development of brain reward circuitry and argue for investigating dynamic relationships among genotype, brain, behavior, and weight throughout development.

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Figures

Figure 1.
Figure 1.
Histograms portraying the number of repeat measurements per child (top) and ages (days) at assessment (bottom) by FTO genotype.
Figure 2.
Figure 2.
A) The blue curve represents the estimated regression coefficient function of the FTO group AT on NAcc volume (as a fraction of global brain volume) growth trajectory with respect to the baseline group TT. The sky-blue band depicts the corresponding bootstrap pointwise 95% confidence interval. B) The red curve represents the estimated regression coefficient function of the FTO group AA on NAcc volume (as a fraction of glocal brain volume) growth trajectory with respect to the baseline group TT. The pink band illustrates the corresponding bootstrap pointwise 95% confidence interval.
Figure 3.
Figure 3.
A) The blue curve depicts the estimated regression coefficient function of the FTO group AT on the frontal lobe brain volume (as a fraction of global brain volume) growth trajectory with respect to the baseline group TT. The sky-blue band represents the corresponding bootstrap pointwise 95% confidence interval. B) The red curve represents the estimated regression coefficient function of the FTO group AA on frontal lobe brain volume (as a fraction of global brain volume) growth trajectory with respect to the baseline group TT (low obesity risk). The pink band illustrates the corresponding bootstrap pointwise 95% confidence interval.
See this image and copyright information in PMC

References

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