The five year research program proposed is focused on basic mechanisms of the genetic determination of obesity, a major health problem that is mediated by behavior. Human obesity has been shown to be under substantial genetic control. The precise mode of genetic inheritance is unknown, and there may be more than one form of genetic obesity. Moderate to extreme obesity is highly familial and may be influenced more strongly by genetic factors than less extreme levels of fatness. Pilot data indicate that both the population distribution and the familial pattern of fatness are consistent with major gene effects on moderate obesity. The proposed genetic study is unique in that it will focus on obesity (40% overweight) as well as on the whole range of human fatness (from fat to lean). Two sets of analyses will be performed. One set of analyses will focus on tests of major gene models for obesity, particularly for homogeneous subgroups of families. Genetic analyses will be conducted of body fatness data already collected on 844 randomly selected families and 1406 families selected through hyperlipidemic index cases from the Lipid Research Clinic Family Study. In this sample, all family members have measures of height, weight, blood chemistry and serum lipid levels. Index cases have these measures as well as reported height and weight at age 18. Analyses will assess whether there are different genetic mechanisms in homogeneous subgroups of families subdivided on the basis of characteristics of the index case, e.g., age at onset, and concomitant hyperlipidemia. A second set of analyses is aimed at identifying patient characteristics which can be used as markers for homogeneous subgroups for genetic studies. The analyses will focus on a separate sample of 450 obese patients to be added to an existing Obesity Research Center database over a three year period, including extensive patient information and family history of obesity for first degree relatives. Tests will be made of the relationship of familial risk for obesity to age at onset, fat distribution (upper vs lower body), response to treatment, metabolic rate, concomitant hyperlipidemia and fat cell number in obese patients. These two sets of related studies will help to identify genetic factors in obesity and target groups with high familial risk for treatment and prevention.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
First Independent Research Support & Transition (FIRST) Awards (R29)
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Psychopathology and Clinical Biology Research Review Committee (PCB)
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University of Pennsylvania
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Price, R A; Charles, M A; Pettitt, D J et al. (1993) Obesity in Pima Indians: large increases among post-World War II birth cohorts. Am J Phys Anthropol 92:473-9
Price, R A; Lunetta, K; Ness, R et al. (1992) Obesity in Pima Indians. Distribution characteristics and possible thresholds for genetic studies. Int J Obes Relat Metab Disord 16:851-7
Price, R A; Ness, R; Sorensen, T I (1991) Changes in commingled body mass index distributions associated with secular trends in overweight among Danish young men. Am J Epidemiol 133:501-10
Ness, R; Laskarzewski, P; Price, R A (1991) Inheritance of extreme overweight in black families. Hum Biol 63:39-52
Price, R A; Gottesman, I I (1991) Body fat in identical twins reared apart: roles for genes and environment. Behav Genet 21:1-7
Price, R A; Ness, R; Laskarzewski, P (1990) Common major gene inheritance of extreme overweight. Hum Biol 62:747-65
Price, R A; Stunkard, A J; Ness, R et al. (1990) Childhood onset (age less than 10) obesity has high familial risk. Int J Obes 14:185-95
Sorensen, T I; Price, R A (1990) Secular trends in body mass index among Danish young men. Int J Obes 14:411-9
Price, R A; Stunkard, A J (1989) Commingling analysis of obesity in twins. Hum Hered 39:121-35
Sorensen, T I; Price, R A; Stunkard, A J et al. (1989) Genetics of obesity in adult adoptees and their biological siblings. BMJ 298:87-90

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