Obesity related phenotypes in families selected for extreme obesity and leanness

Abstract

BACKGROUND: Obesity is a multigenic trait, and special methods and sampling designs are needed for gene identi®cation. OBJECTIVE: To describe characteristics of families selected to increase information for genetic linkage studies of obesity. DESIGN: Families having extremely obese siblings with a lean parent and sibling. SUBJECTS: 594 members of 94 Caucasian families. MEASUREMENTS: Measured height and weight, bioelectric impedance, skinfolds, circumferences and questionnaires. RESULTS: Families have an extreme range of obesity phenotypes, which are bimodally distributed. The obese individuals are predominantly women with an onset of obesity early in life. Obesity onset age was negatively correlated with level of obesity, and onset ages were correlated among family members. Individual obesity measures were highly correlated. The extreme range of phenotypes within families increases family variability and presumably gene segregation. CONCLUSION: Sampling families through extremely obese sibling pairs with a lean parent and sibling results in families with an extreme range of obesity and leanness. The large within-family variance and early age of onset should make these families highly informative for gene mapping and gene identi®cation studies.

Leptin resistance is associated with extreme obesity and aggregates in families

“…Because plasma leptin concentrations are highly correlated with BMI and BMI is heritable, this observation is expected. However, the families studied here were selected for extreme discordance in body weight, 7 and so the familial aggregation of plasma leptin concentration was surprising. Other studies using families unselected for obesity variables 8 -10 found additive genetic effects ranging from 39 to 73% for plasma leptin, but the familial similarity for leptin was largely due to the familial aggregation of BMI.…”

“…A detailed description of the characteristics of the study participants was presented in a previous paper. 7 To be included in the study, probands must have a body mass index (BMI; weight (kg)=height (m 2 )) greater than or equal to 40 kg=m 2 , have one or more siblings with a current BMI greater than or equal to 30 kg=m 2 , one or more siblings must have a maximum lifetime BMI less than 27 kg=m 2 , and at least one parent must have a maximum lifetime BMI less than 27 kg=m 2 .…”

Estimates of the heights and weights of family members: accuracy of informant reports

“…The assessment procure also included direct measurement of standing height (cm) and weight (lb) while the subject was wearing socks and a hospital gown or light clothing. 7 Weights were converted from pounds to kilograms prior to analysis. Family members completed their questionnaires prior to being measured.…”

Interaction between obesity-susceptibility loci in chromosome regions 2p25-p24 and 13q13-q21

“…The recruitment processes have been described previously. 26,27 After obtaining informed consent, the probands and their biological parents and full siblings were measured for weight, height, waist circumference, percent body fat and other anthropometric measurements. Blood samples were also collected.…”