Environmental and Genetic Risk Factors in Obesity

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Because of its high prevalence and the associated medical and psychosocial risks, research into the causes of childhood obesity has experienced a tremendous upswing. Formal genetic data based on twin, adoption, and family studies lead to the conclusion that at least 50% of the interindividual variance of the body mass index (BMI; defined as weight in kilograms divided by height in meters squared) is due to genetic factors. As a result of the recent advent of genome-wide association studies, the first polygenes involved in body weight regulation have been detected. Each of the predisposing alleles explain a few hundred grams of body weight. More polygenes will be detected in the near future, thus for the first time allowing in-depth analyses of gene–gene and gene–environment interactions. They also will enable developmental studies to assess the effect of such alleles throughout childhood and adulthood. The recent increase in obesity prevalence rates illustrates the extreme relevance of environmental factors for body weight. Similar to polygenes, the effect sizes of most such environmental factors are likely to be small, thus rendering their detection difficult. In addition, the validation of the true causality of such factors is not a straightforward task. Important factors are socioeconomic status and television consumption. The authors conclude by briefly assessing implications for treatment and prevention of childhood obesity.

Section snippets

Formal genetic aspects

There is a general consensus that parental obesity is by far the strongest risk factor for childhood and adolescent obesity. The degree of parental obesity influences this risk, which is further elevated if both parents are obese.17, 18 According to several studies, offspring BMI is somewhat more strongly correlated with maternal than paternal BMI,19 suggesting intrauterine influences, imprinting effects, an influence of mitochondrial genes, or a rearing effect. Formal genetic studies have led

Syndromal Obesity

The Prader–Willi syndrome (PWS) is caused by the deficiency of one or more paternally expressed imprinted transcripts within chromosome 15q11-q13, including SNURF-SNRPN and multiple small nucleolar RNAs (snoRNAs). Recently, a microdeletion of the HBII-85 snoRNAs in a child with the typical features of the PWS provided conclusive evidence that deficiency of HBII-85 snoRNAs causes the key characteristics of the PWS phenotype.34 The pleiotropic Bardet–Biedel syndrome, of which obesity is a

Environmental factors

Secular changes in energy intake and expenditure are assumed to underlie the obesity epidemic.30 However, attempts to unequivocally pinpoint the relevant mechanisms, even within a single country or society, have been largely futile. Controversy exists as to the proportional contribution of an elevated energy intake in comparison to a reduced energy expenditure due to the modern-day sedentary lifestyle. In England, energy intake counterintuitively seemingly declined between 1970 and 1990;61

Summary

Disentangling the diverse mechanisms underlying variation of BMI and, in particular, overweight and obesity is proving exceedingly difficult. The advent of GWA will continue to enable the detection of polygenes. DNA of tens of thousands individuals is required to validate an initial finding, thus illustrating the small effect sizes. Complex interactions between genes and environmental factors can be assumed to occur.

Treatment of obesity is difficult in both children and adults. Whereas weight

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      Obesity is associated with increased risk for a variety of serious medical conditions, including heart disease, stroke, and Type 2 diabetes, as well as substantial medical costs (Chu et al., 2018) and premature death (Hu et al., 2004). Although multiple factors have been identified that increase risk for obesity (e.g., genetics, sedentary behavior, socioeconomic status; Hebebrand & Hinney, 2009; Rhodes et al., 2012; Waalen, 2014), considerable attention has been placed on the role of sugar consumption – a malleable and frequent target of public health obesity prevention campaigns (e.g., Bradley et al., 2020; Farley et al., 2017; Siervo et al., 2014; Stanhope, 2016). Increased sugar consumption is associated with the greater prevalence of obesity (Siervo et al., 2014), and studies have shown a clear dose-response relationship between the intake of sugar-sweetened beverages in particular and risk for obesity and Type 2 diabetes (see Harrington, 2008; Hu, 2013).

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