Obesity: choosing genetic approaches from a mixed menu.

Obesity, as defined by any number of metrics, aggregates in families but does not segregate as a simple Mendelian trait. Because of the frequent association of obesity with a number of common chronic diseases, researchers are greatly interested in identifying the genes that contribute to obesity and their mode of action. The lack of a consensus regarding the biological basis of obesity makes the selection of appropriate candidate genes difficult. Several approaches to selecting plausible candidate genes for the study of obesity are outlined here. The study of rare human phenotypes that result in extreme obesity may identify genes that through polymorphic genetic variation may have an effect on body mass, body composition, or fat distribution. The study of human genes homologous to the mouse genes that lead to obesity in particular strains of inbred mice may also give clues to the location and identity of obesity-related genes. Human populations in which obesity is particularly prevalent may serve as a substrate for identifying such genes in the general population.