Genetics of Obesity in Humans: Current Issues

During the last decade, we have begun to understand some of the reasons why people become obese as assessed by excess body mass for height or excess total body fat content. Obesity frequently aggregates in families. However, this familial resemblance is caused not only by genetic effects but also by lifestyle, and environmental and cultural factors. Thus the genetic heritability of the obesity phenotypes accounts for up to 50% of the age- and gender-adjusted phenotypic variances. These results have been confirmed by overfeeding and negative energy balance studies. The effects of single segregating genes can be detected only under the correct experimental conditions. Most scientists in the area believe that these genes can be identified and that the DNA mutations associated with human obesities will be uncovered. Indeed, association and linkage studies, quantitative trait loci and positional cloning research strategies, and transgenic mouse models are sufficiently promising to suggest that these aims can be achieved. A review of the evidence reported thus far reveals that there are already four loci with strong evidence of linkage with obesity phenotypes in humans.