How much of obesity is genetic?

Given that the explosion in obesity prevalence over the past 20 years is likely to have taken place against a background of relatively constant population genetic structure, the question of to what extent obesity is subject to genetic influence is one that merits careful consideration. Many studies have attempted to resolve the population variance of a specific obesity phenotype into genetic, environmental and unknown (or residual) effects.

In principle, the total observed phenotypic variance, V_p may be considered to be due to the sum of genetic variance (V_g ), shared environmental variance (V_c ) and an unknown residual (unshared environmental) variance (V_e ) such that V_p = V_g + V_c + V_e . The percentage genetic inheritability of the trait in question is represented by the term V_g /V_p. Modifications of this simple model to attempt detection of gene–gene and gene–environment interactions and the application of complex multivariate computational modelling in different study populations are reviewed in detail elsewhere (Bouchard et al., 1998).

Twin studies

Twin studies allow separation of genetic and environmental components of variance since monozygotic (MZ) twins share 100 per cent of their genes whilst non-identical dizygotic (DZ) twins share 50 per cent on average. The fact that there is discordance in the prevalence of obesity between MZ and DZ twins raised together supports the concept of genetic heritability of obesity if it is assumed that twins share exactly the same environmental influences (although it has been suggested that MZ twins may share more environmental influences than DZ twins; Hebebrand et al., 2001). Total genetic variance may then be subdivided into two components; additive variance, which results from the sum of contributions of many alleles at different loci and non-additive effects, which are principally determined by the dominance of one allele over another at the same locus. It follows that an additive model is suggested when intrapair correlations of DZ twins are half that of MZ twins and a non-additive model is suggested when DZ twins have substantially less than half the intrapair correlations of variance of MZ twins.

Comparison of MZ twins raised together with MZ twins raised apart probably represent the ideal study group. However, such study populations are difficult to find and, even then, twins will have shared the same intra-uterine environment (which may be important on the basis of the Barker hypothesis; Hales and Barker, 1992). Furthermore, there may be indirect genetic effects in operation and the effect of environment may be underestimated as certain environmental conditions are likely to be common to both twins (e.g. the general availability of fast foods).

One study (Stunkard et al., 1986) assessed body mass index in a sample of 1974 MZ and 2097 DZ male twin pairs and found concordance in MZ twins to be around 0.8. This was twice as high as that in DZ twins both at age 20 and at 25 year follow up. Others (Fabsitz et al., 1992), however, report an age-specific effect such that only 40 per cent of the genetic factors that influence body weight at the age of 20 continue to do so by the age of 48.