I blame my parents for my waistline. But is this genetic alibi valid?
Roy J. Shephard1
Objective. The objectives of this narrative review are to consider the contribution of inherited factors to the development of obesity and its response to treatment, and the extent to which an adverse inheritance provides a "genetic alibi" to those who are obese. Methods. Information obtained from Ovid/Medline and Google Scholar through to December 2018 was supplemented by a search of the author's extensive personal files. Results. Animal models demonstrate that specific single genetic mutations can cause severe obesity, as in ob/ob and db/db mice and in the Zucker fatty rat. In humans, also, traditional genetic studies of adopted children, twins and entire families point to a substantial contribution of inheritance to such measures of obesity as BMI. However, perhaps because of a lesser impact of a shared family environment, estimates of heritability coefficients are substantially smaller for family studies (a 50th percentile coefficient of 0.46) than for twin studies (a 50th percentile coefficient of 0.75). Estimates of heritability vary widely for both approaches, with populations that are faced by an obesogenic environment tending to show higher values for coefficients derived from either type of data set. Attempts to link such heritability estimates to specific genetic sites have as yet been able to account for less than 5% of the total inter-individual variation in BMI. The main probable factors limiting the discovery of relevant chromosomal sites are a polygenic rather than monogenic basis for obesity and a strong modification of gene expression by epigenetic influences. Conclusions. Inherited factors appear to make a substantial contribution to the accumulation of body fat. Nevertheless, the validity of the "genetic alibi" is weakened in that dietary moderation and regular physical activity can greatly limit the phenotypic expression of obesity-inducing genetic characteristics.
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