Mini-Review: The Contribution of Intermediate Phenotypes to GxE Effects on Disorders of Body Composition in the New OMICS Era

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Abstract

Studies of gene-environment (GxE) interactions describe how genetic and environmental factors influence the risk of developing disease. Intermediate (molecular or clinical) phenotypes (IPs) are traits or metabolic biomarkers that mediate the effects of gene-environment influences on risk behaviors. Functional systems genomics discovery offers mechanistic insights into how DNA variations affect IPs in order to detect genetic causality for a given disease. Disorders of body composition include obesity (OB), Type 2 diabetes (T2D), and osteoporosis (OSTP). These pathologies are examples of how a GxE interaction contributes to their development. IPs as surrogates for inherited genotypes play a key role in models of genetic and environmental interactions in health outcomes. Such predictive models may unravel relevant genomic and molecular pathways for preventive and therapeutic interventions for OB, T2D, and OSTP. Annotation strategies for genomes, in contrast to phenomes, are well advanced. They generally do not measure specific aspects of the environment. Therefore, the concepts of deep phenotyping and the exposome generate new avenues to exploit with high-resolution technologies for analyzing this sophisticated phenome. With the successful characterization of phenomes, exposomes, and genomes, environmental and genetic determinants of chronic diseases can be united with multi-OMICS studies that better examine GxE interactions.

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Most cited references 40

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Mechanisms of disease: is osteoporosis the obesity of bone?

Clifford Rosen, Mary Bouxsein (2006)

Osteoporosis and obesity, two disorders of body composition, are growing in prevalence. Interestingly, these diseases share several features including a genetic predisposition and a common progenitor cell. With aging, the composition of bone marrow shifts to favor the presence of adipocytes, osteoclast activity increases, and osteoblast function declines, resulting in osteoporosis. Secondary causes of osteoporosis, including diabetes mellitus, glucocorticoids and immobility, are associated with bone-marrow adiposity. In this review, we ask a provocative question: does fat infiltration in the bone marrow cause low bone mass or is it a result of bone loss? Unraveling the interface between bone and fat at a molecular and cellular level is likely to lead to a better understanding of several diseases, and to the development of drugs for both osteoporosis and obesity.

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Obesity: overview of an epidemic.

Nia Mitchell, Victoria A Catenacci, Holly Wyatt … (2011)

The obesity epidemic in the United States has proven difficult to reverse. We have not been successful in helping people sustain the eating and physical activity patterns that are needed to maintain a healthy body weight. There is growing recognition that we will not be able to sustain healthy lifestyles until we are able to address the environment and culture that currently support unhealthy lifestyles. Addressing obesity requires an understanding of energy balance. From an energy balance approach it should be easier to prevent obesity than to reverse it. Further, from an energy balance point of view, it may not be possible to solve the problem by focusing on food alone. Currently, energy requirements of much of the population may be below the level of energy intake than can reasonably be maintained over time. Many initiatives are underway to revise how we build our communities, the ways we produce and market our foods, and the ways we inadvertently promote sedentary behavior. Efforts are underway to prevent obesity in schools, worksites, and communities. It is probably too early to evaluate these efforts, but there have been no large-scale successes in preventing obesity to date. There is reason to be optimistic about dealing with obesity. We have successfully addressed many previous threats to public health. It was probably inconceivable in the 1950s to think that major public health initiatives could have such a dramatic effect on reducing the prevalence of smoking in the United States. Yet, this serious problem was addressed via a combination of strategies involving public health, economics, political advocacy, behavioral change, and environmental change. Similarly, Americans have been persuaded to use seat belts and recycle, addressing two other challenges to public health. But, there is also reason to be pessimistic. Certainly, we can learn from our previous efforts for social change, but we must realize that our challenge with obesity may be greater. In the other examples cited, we had clear goals in mind. Our goals were to stop smoking, increase the use of seatbelts, and increase recycling. The difficulty of achieving these goals should not be minimized, but they were clear and simple goals. In the case of obesity, there is no clear agreement about goals. Moreover, experts do not agree on which strategies should be implemented on a widespread basis to achieve the behavioral changes in the population needed to reverse the high prevalence rates of obesity. We need a successful model that will help us understand what to do to address obesity. A good example is the recent HEALTHY study. This comprehensive intervention was implemented in several schools and aimed to reduce obesity by concentrating on behavior and environment. This intervention delivered most of the strategies we believe to be effective in schools. Although the program produced a reduction in obesity, this reduction was not greater than the reduction seen in the control schools that did not receive the intervention. This does not mean we should not be intervening in schools, but rather that it may require concerted efforts across behavioral settings to reduce obesity. Although we need successful models, there is a great deal of urgency in responding to the obesity epidemic. An excellent example is the effort to get menu labeling in restaurants, which is moving rapidly toward being national policy. The evaluation of this strategy is still ongoing, and it is not clear what impact it will have on obesity rates. We should be encouraging efforts like this, but we must evaluate them rigorously. Once we become serious about addressing obesity, it will likely take decades to reverse obesity rates to levels seen 30 years ago. Meanwhile, the prevalence of overweight and obesity remains high and quite likely will continue to increase.

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Diabetes and Its Effect on Bone and Fracture Healing.

Hongli Jiao, E Xiao, Dana Graves (2015)

Diabetes mellitus is a metabolic disorder that increases fracture risk, interferes with bone formation, and impairs fracture healing. Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) both increase fracture risk and have several common features that affect the bone including hyperglycemia and increased advanced glycation end product (AGE) formation, reactive oxygen species (ROS) generation, and inflammation. These factors affect both osteoblasts and osteoclasts leading to increased osteoclasts and reduced numbers of osteoblasts and bone formation. In addition to fracture healing, T1DM and T2DM impair bone formation under conditions of perturbation such as bacteria-induced periodontal bone loss by increasing osteoblast apoptosis and reducing expression of factors that stimulate osteoblasts such as BMPs and growth factors.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Environ Res Public Health

Journal ID (iso-abbrev): Int J Environ Res Public Health

Journal ID (publisher-id): ijerph

Title: International Journal of Environmental Research and Public Health

Publisher: MDPI

ISSN (Print): 1661-7827

ISSN (Electronic): 1660-4601

Publication date (Electronic): 17 September 2017

Publication date (Print): September 2017

Volume: 14

Issue: 9

Electronic Location Identifier: 1079

Affiliations

[1 ]Facultad de Salud Pública y Nutrición (FASPyN), Universidad Autónoma de Nuevo León, Monterrey 64290, Mexico; ednajnava@ 123456hotmail.com

[2 ]Facultad de Enfermería, Universidad Autónoma de Nuevo León, Monterrey 64290, Mexico; esther.gallegosc@ 123456gmail.com

[3 ]Facultad de Medicina y Ciencias Biomédicas, Universidad Autónoma de Chihuahua, México 31110, Mexico; ilealb62@ 123456yahoo.com.mx

[4 ]Department of Genetics and Southwest National Primate Center, Texas Biomedical Research Institute, San Antonio, TX 78227, USA

Author notes

[* ]Correspondence: raul@ 123456TxBiomed.org ; Tel.: +1-210-258-9731

Article

Publisher ID: ijerph-14-01079

DOI: 10.3390/ijerph14091079

PMC ID: 5615616

PubMed ID: 28926971

SO-VID: 853bd393-accc-403f-991c-8cba19d2e75b

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Mini-Review: The Contribution of Intermediate Phenotypes to GxE Effects on Disorders of Body Composition in the New OMICS Era

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Abstract

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Karger: Nutrition and Dietetics

Most cited references 40

Mechanisms of disease: is osteoporosis the obesity of bone?

Obesity: overview of an epidemic.

Diabetes and Its Effect on Bone and Fracture Healing.

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