Obesity as a disease state or adiposity as a continuous variable

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Obesity as a clinical condition is currently defined as an excess accumulation of adipose tissue resulting in a BMI greater than 30kg/m2. While the diagnosis of obesity by this criterion has clinical relevance with regards to intervention, management, and treatment, from an epidemiological perspective, it may hamper the study of the genetics underlying variation in body fat mass and distribution. For example, BMI exhibits a normal distribution with no clear division between the ''clinically obese" (BMI >30) and the non-obese. Such a pattern of continuous distribution is not restricted to merely BMI but is found in all obesity-related phenotypes, including anthropo-metric measures (e.g. skin folds, and waist circumference), measures of body composition (e.g. percentage body fat, fat mass), and associated biochemical markers (e.g. leptin). Therefore the division of individuals into ''obese'' versus ''non-obese'' categories has a certain degree of arbitrariness that does not appear to follow any underlying biological effect (which might be due to the effect of a gene/genes). A complex phenotype by definition is a quantifiable characteristic that is influenced by both multiple genetic and non-genetic factors as well as their interactions, leading to variation in expression across the population. Thus the use of a definition, which takes continuously distributed measures and converts them to such dichotomous states as ''obese'' vs. ''not obese,'' may actually hinder attempts to identify genes influencing complex phenotypes by greatly decreasing statistical power. Significant information may be lost in the transition from a continuous to a discontinuous scale and these issues need to be considered when selecting the appropriate method for genetic analyses of these traits (Comuzzie etal., 2001).

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