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FTO association and interaction with time spent sitting.

Y C Klimentidis1, A Arora1, A Chougule1

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The FTO gene variant influences body mass index (BMI) by affecting time spent sitting (TSS). This genetic factor partially mediates BMI through sedentary behavior, highlighting the link between genetics and obesity.

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Area of Science:

  • Genetics and Obesity Research
  • Human Physiology and Metabolism

Background:

  • The FTO gene variant is known to interact with physical activity to influence body mass index (BMI).
  • Sedentary behavior, specifically time spent sitting (TSS), is increasingly recognized as a significant risk factor for obesity and associated health conditions.

Purpose of the Study:

  • To investigate the potential interaction between the FTO gene and time spent sitting (TSS) in relation to body mass index (BMI).
  • To determine if the FTO gene's effect on BMI is mediated by TSS.

Main Methods:

  • Analysis of two Framingham Heart Study (FHS) cohorts (n=3430 and n=3888) and replication in the Women's Health Initiative (WHI) cohort (n=4756).
  • Examination of the association between FTO genotype and TSS, and the interaction between FTO and TSS on BMI, adjusting for covariates like physical activity.

Main Results:

  • A significant positive association was observed between the BMI-increasing FTO allele and TSS in the FHS cohort, with a similar trend in WHI.
  • Mediation analyses indicated that the FTO gene's effect on BMI is partly mediated through TSS.
  • A significant interaction between FTO and TSS on BMI was found in FHS, but not in the meta-analysis of FHS and WHI, suggesting complex interplay.

Conclusions:

  • The FTO gene appears to influence BMI, in part, through energy expenditure mechanisms related to time spent sitting (TSS).
  • Further research is recommended to explore the interplay between genetic factors, sedentary behavior, and obesity-related outcomes.