Familial risk ratios for extreme obesity: implications for mapping human obesity genes

OBJECTIVE: To determine familial risk ratios for extreme obesity to aid in the design of obesity linkage studies. DESIGN: Family study of obesity SUBJECTS: 2349 first-degree relatives (parents and siblings) of 840 probands who are members of the National Association to Advance Fat Acceptance (NAAFA) and 5851 participants of the first phase of the National Health and Nutrition Examination Survey III. METHODS: Computed age–gender standardized risk ratios (SRRs) for obesity in relatives categorized by the level of obesity in the index case (proband). MEASUREMENT: Body mass index (BMI) (kg/m2) RESULTS: The risk of extreme obesity (BMI≥40) in relatives of extremely obese women (BMI≥40) was more than five times greater than in the population; furthermore, the risk of obesity in relatives was approximately linearly associated with the degree of obesity in the proband. The risk of thinness in relatives of obese individuals was substantially lower than in the general population. CONCLUSION: Because the familial risk ratio for extreme obesity is higher than for moderate levels of obesity, the number of families required to achieve adequate statistical power in gene mapping studies of obesity can be reduced substantially by focusing on family members of extremely obese individuals (BMI≥40).