The concepts of gene-behavior and gene-environment interactions of Obesity

The concepts of gene-behavior and gene-environment interactions of Obesity
The major themes of state-of-the-science research focused on gene-environment behavior interactions and propose future research directions in obesity research. Fulfilling the research recommendations outlined in the last section will require transdisciplinary research teams representing behavioral science, genetics, nutrition, exercise science, epidemiology, and biostatistics. The future  obesity research  demonstrates the need for collaborative and transdisciplinary approaches, and will serve as a catalyst for the development of partnerships and collaborations. The incorporate gene-behavior and gene-environment interaction components in their studies to improve our understanding of the complex network of factors that contribute to obesity risk, and in the process will aid in both control and prevention of lifestyle behaviors related to chronic diseases and cancer.

GENE-BEHAVIOR INTERACTIONS

  • The concepts of gene-behavior and gene-environment interactions are critical. There is a synergistic relationship among genes, behavior, and the environment. When individuals living in a “restrictive” environment evolve toward an obesogenic environment, such as that found in industrialized countries, most are likely to gain weight. However, those with a high genetic predisposition for obesity will gain the most weight, whereas those resistant to obesity will gain little, if any, weight. The findings reported to date and how to undertake more powerful studies of gene-behavior and gene environment interaction effects are the focus of the workshop papers published in this supplement issue of Obesity.
  • Knowledge of the human genome has grown exponentially in the past several years. Exploration of gene-gene, gene-behavior, and gene-environment interactions as they relate to health and disease can now be undertaken with more powerful tools than ever before. In 2006, the National Institutes of Health implemented the Genes, Environment, and Health Initiative, which promotes both genetic analysis and the development of new tools to measure environmental exposures that affect health (http://genesandenvironment.nih.gov)
  • The development of innovative technologies to measure environmental exposures and behaviors such as diet and physical activity should be a priority, as they will greatly contribute to advancing gene behavior research.
  • The influence of genetic, environmental, and behavioral factors on the relationship between obesity and cancer has been identified as a priority scientific area for the National Cancer Institute (NCI). The 2008 NCI Strategic Plan highlighted the need to “increase our understanding of behavioral, environmental, genetic, and epigenetic causes of cancer and how they interact. ” Using the plan as the impetus, in September 2007 the NCI Division of Cancer Control and Population Sciences (DCCPS) sponsored a workshop, Gene-Nutrition and Gene-Physical Activity Interactions in the Etiology of Obesity. Leading scientists representing various disciplines were convened to assess the state of the science and to evaluate the current understanding of gene-environment-behavior interactions as they relate to obesity risk and to identify research priorities and future directions.

Gene-environment-behavior studies in obesity research.
Multidisciplinary perspective and raise important questions as to how to conduct gene-environment-behavior studies in obesity research. The supplement includes 16 articles that cover a range of topics, from genetics studies using animal models to prevention and treatment of obesity in humans. The final article  highlights the research recommendations discussed in the last workshop session. Bouchard et all defines gene-environment and gene-behavior interactions, discusses study design issues, and examines what is currently known about obesity and obesity-related genes. 

  1. Lenard and Berthoud is devoted to the pathways and genes involved in the central and peripheral regulation of food intake and physical activity. 
  2. Reed and Ordovas address gene-nutrition interaction. Reed discusses how animal models can be used to examine genetic determinants of food preferences
  3. Ordovas focuses on nutritional genomics and gene-nutrient interactions in the prevention of chronic diseases
  4. Chung and Leibel et all review human and animal studies relevant to the genetics of obesity. Specifically, they discuss the role of genes in regulating body weight and response to nutrient excess and deficiency. Levin  examines epigenetic influences on food intake and physical activity. Using an animal model, he illustrates how manipulations in the perinatal environment can permanently alter the system that regulates energy homeostasis.

Two articles address gene-physical activity interactions. 

  1. Koch and Britton describe the use of an animal model to explore mechanistic gene-environment interactions for aerobic capacity and risk for disease. 
  2. Rankinen and Bouchard discuss heterogeneity in responsiveness to standardized behavioral changes and how genotype may influence this response in humans.

Epidemiological study designs and strategies for investigating how gene-behavior interactions lead to weight gain

  • Wareham, Young, and Loos , who emphasize the importance of precise measurement tools to accurately assess the exposure and outcome of interest. 
  • Bray explores the implications of gene-environment-behavior interactions in obesity prevention and intervention studies. She also discusses whether genes in pathways controlling energy balance and adipogenesis influence the results of weight-loss programs.

In the spirit of a broad and transdisciplinary approach to understanding gene-environment-behavior interactions, several leading researchers were asked to serve as discussants after the presentations. Those important perspectives are included in this supplement. 

  • Dishman and Faith. Dishman discusses the importance of using motivational traits or social-cognitive mediators when studying physical activity behaviors. He also advocates using multilevel statistical modeling of personal, environmental, and genetic influences on physical activity. 
  • Faith  discusses opportunities for behavioral scientists to become involved in designing behavioral “challenges” in experiments, determining behavioral phenotypes for genetics studies, and identifying specific measures of the environment or environmental exposures for studies of gene-behavior interactions.

To complement the behavioral perspective, genetic research discussants were invited to provide comments. 

  • Warden and Fisler summarize the conference presentations and the barriers that must be overcome before individual diet and exercise recommendations can be made on the basis of genotype. 
  • Shuldiner summarizes the field’s current understanding of energy homeostasis and offers recommendations for translating our limited genetic knowledge into more effective modalities for treatment and prevention.
  • Agurs-Collins and colleagues discuss public health genomics as a framework for translating obesity genomics research into clinical and public health practice. Common challenges for gene-environment-behavior research, as outlined in the articles, include study design, measurement precision in assessing behavioral phenotypes, sample sizes large enough to achieve adequate statistical power, and technologies to accurately measure behavioral and environmental exposure.

References

  • Bouchard C, Agurs-Collins T. Studying gene-behavior interactions:summary of recommendations. Obesity. 2008;16 Supp 3:S85–S86. 
  • Bouchard C. Gene-environment interactions in the etiology of obesity:defining the fundamentals. Obesity. 2008;16 Supp 3:S5–S10.
  • Lenard NR, Berthoud H-R. Central and peripheral regulation of food intake and physical activity: pathways and genes. Obesity. 2008;16 Supp 3:S11–S22. 
  • Reed DR. Animal models of gene-nutrient interactions. Obesity. 2008;16 Supp 3:S23–S27. 
  • Ordovas JM. Genotype-phenotype associations: modulation by diet and obesity. Obesity. 2008;16 Supp 3:S40–S46. 
  • Chung WK, Leibel RL. Considerations regarding the genetics of obesity. Obesity. 2008;16 Supp 3:S33–S39. 
  • Levin BE. Epigenetic influences on food intake and physical activity level:review of animal studies. Obesity. 2008;16 Supp 3:S51–S54.
  • Koch LG, Britton SL. Development of animal models to test the fundamental basis of gene-environment interactions. Obesity. 2008;16 Supp 3:S28–S32.
  • Rankinen T, Bouchard C. Gene-physical activity interactions: overview of human studies. Obesity. 2008;16 Supp 3:S47–S50.
  • Wareham NJ, Young EH, Loos RJF. Epidemiological study designs to investigate gene-behavior interactions in the context of human obesity. Obesity. 2008;16 Supp 3:S66–S71.
  • Bray M. Implications of gene-behavior interactions: prevention and intervention for obesity. Obesity. 2008;16 Supp 3:S72–S78.
  • Dishman RK. Gene-physical activity interactions in the etiology of obesity:behavioral considerations. Obesity. 2008;16 Supp 3:S60–S6
  • Faith MS. Behavioral science and the study of gene-nutrition and genephysical activity interactions in obesity research. Obesity. 2008;16 Supp 3:S82–S84. 
  • Warden CH, Fisler JS. Gene-nutrient and gene-physical activity summary–genetics viewpoint. Obesity. 2008;16 Supp 3:S55–S59.
  • Shuldiner AR. Obesity genes and gene-environment-behavior interactions:recommendations for a way forward. Obesity. 2008;16 Supp 3:S79–S81. 
  • Agurs-Collins T, Khoury MJ, Simon-Morton D, et al. Public health genomics: translating obesity genomics research into population health benefits. Obesity. 2008;16 Supp 3:S87–S96. 
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