Genetics of Childhood Obesity

Hindawi Publishing Corporation Journal of Obesity Volume 2011, Article ID 845148, 9 pages doi:10.1155/2011/845148 Review Article Genetics of Childhood Obesity Jianhua Zhao1 and Struan F. A. Grant1, 2, 3 1 Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA 2 Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA 3 Center for Applied Genomics, Abramson Research Center, The Children’s Hospital of Philadelphia Research Institute, 34th and Civic Center Boulevard, Philadelphia, PA 19104, USA Correspondence should be addressed to Struan F. A. Grant, Received 30 November 2010; Accepted 6 April 2011 Academic Editor: Andrew P. Hills Copyright © 2011 J. Zhao and S. F. A. Grant. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Obesity is a major health problem and an immense economic burden on the health care systems both in the United States and the rest of the world. The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. Genomewide association studies (GWAS) have revealed strongly associated genomic variants associated with most common disorders; indeed there is general consensus on these findings from generally positive replication outcomes by independent groups. To date, there have been only a few GWAS-related reports for childhood obesity specifically, with studies primarily uncovering loci in the adult setting instead. It is clear that a number of loci previously reported from GWAS analyses of adult BMI and/or obesity also play a role in childhood obesity. 1. Definition and Epidemiology of Childhood Obesity Obesity is a major health problem in modern societies, with a prevalence of up to 25% in Western societies and an increasing incidence in children [1]. Obesity, plus the associated insulin resistance [2, 3], is also considered a contributor to the major causes of death in the United States and is an important risk factor for type 2 diabetes (T2D), cardiovascular diseases (CVD), hypertension, and other chronic diseases. Approximately 70% of obese adolescents grow up to become obese adults [4–6]. The main direct adverse effects of childhood obesity include orthopedic complications, sleep apnea, and psychosocial disorders [7, 8]. Obesity present in adolescence has been shown to be associated with increased overall mortality in adults [9]; overweight children followed up for 40 [10] and 55 years [11] were more likely to have CVD and digestive diseases, and to die from any cause as compared with those who were lean. Obesity is a complex disease that involves interactions between environmental and genetic factors. Excess in adipose tissue mass can be seen as a disruption in the balance between energy intake and expenditure. In modern times, this excess in adipose tissue fuel storage is considered a disease; however, a better viewpoint would be that obesity is a survival advantage that has gone astray that is, what is now considered a disease was probably advantageous when food was less available and a high level of energy expenditure through physical activity was a way of life [12]. The true prevalence of childhood obesity is difficult to empirically quantify as there is currently no internationally accepted definition; however, in general terms, childhood obesity is considered to have reached epidemic levels in developed countries. Approximately 25% of children in the US are overweight and approximately 11% are obese. In the 10-year period between the National Health and Nutrition Examination Survey (NHANES) II (1976–1980) and NHANES III (1988– 1991), the prevalence of overweight children in the USA had increased by approximately forty percent [1]. Examination of historical standards for defining overweight in children from many countries tells us that the distribution of BMI is becoming increasingly skewed [13]. The lower part of the distribution has shifted relatively little whereas the upper 2 part has widened substantially. This finding suggests that many children may be more susceptible (genetically or socially) to influence by the changing environment. Although the definition of obesity and overweight has changed over time [14, 15], it can be defined as an excess of body fat. The definition of childhood obesity continues to be problematic due to the fact that almost all definitions use some variant of BMI (body mass index). A range of other methods are available which allow for accurate estimates of total body fat; however, none of these are widely available and/or are easily applicable to the clinical situation. Body weight is reasonably well correlated with body fat but is also highly correlated with height, and children of the same weight but different heights can have widely differing amounts of adiposity, but in adults BMI correlates more strongly with more specific measurements of body fat, that is, BMI is useful for depicting overweight in the population but is an imperfect approximation of excess adiposity [16]. In addition, the relation between BMI and body fat in children varies widely with age and with pubertal maturation. This in itself makes BMI definitions of overweight for children more complex than definitions for adults, which use a single cutoff value for all ages. Definitions of overweight that use BMI-for-age can be based on a number of different standards that all give slightly different results, and all are essentially statistical not functional definitions. However, useful percentile charts relating BMI to age have now been published in several countries [17]. The Center for Disease Control and Prevention defined overweight as at or above the 95th percentile of BMI for age and “at risk for overweight” as between 85th to 95th percentile of BMI for age [18, 19]. European researchers classified overweight as at or above 85th percentile and obesity as at or above 95th percentile of BMI [20]. A recent report from the Institute of Medicine has specifically used the term “obesity” to characterize BMI ≥ 95th percentile in children and adolescents [21]. By late adolescence, these percentiles approach those used for adult definitions; the 95th percentile is then approximately 30 kg/m2 [8]. These statistical percentile definitions are now general guidelines for clinicians and others [19]. 2. Therapeutic Options Data supporting the use of pharmacological therapy for pediatric overweight are limited and inconclusive [22]. Sibutramine has been studied in a randomized controlled trial of severe obesity [23]. It has been shown to be efficacious as compared with behavior therapy alone, but it may be associated with side effects including (...truncated)