The role of genetic analyses in characterizing obesity

To understand how genetic and environmental factors could interact to lead to different types of obesity, a simple hypothetical model is examined involving two genes and one environmental factor. Separate and interactive effects are illustrated. The confounded expression of distant phenotypes and advantages of studying phenotypes close to immediate gene products are explained. The appearance of population frequency distribution curves for level of obesity are illustrated for five different situations simulating actual data behaving according to the hypothetical model. Six suggestions are given as a practical approach to characterizing morbid obesity: (1) describe the frequency distribution of morbid obesity by age and sex in the general population; (2) obtain accurate family history data from obese probands, spouses, and controls; (3) contrast results of metabolic studies between obese probands with and without a family history of obesity; (4) obtain metabolic screening data from close relatives of selected obese probands and controls; (5) study special settings (twins, adoption, migration, race); (6) when justified, perform extensive pedigree studies using metabolic evaluations, linkage markers, and carefully prepared computer model testing. Careful collection of family history data is explained in detail and is proposed as an important and relatively inexpensive tool that should be part of any study of human obesity.