EVIDENCE FOR MULTIPLE DETERMINANTS OF THE BODY-MASS INDEX - THE NATIONAL-HEART,-LUNG,-AND-BLOOD-INSTITUTE FAMILY HEART-STUDY

The body mass index (BMI) is a complex phenotype representing the amou nt of fat mass, lean mass, body build and proportions, and it is likel y to be affected by various metabolic processes, hormonal effects, ene rgy intake and expenditure, and interactions within and among these br oad categories of etiologic factors. Nonetheless, several previous stu dies have reported evidence for major gene segregation for the BMI in various populations. Data on a random sample of Caucasian families par ticipating in the National Heart, Lung, and Blood Institute (NHLBI) Fa mily Heart Study were analyzed to document the extent of familial rese mblance and to investigate whether a similar monogenic inheritance pat tern could be detected. Genetic analysis was carried out on age- and s ex-adjusted BMI values. Familial correlations mere significant implyin g a maximal heritability, including all genetic and environmentally in herited additive factors, of 41% to 59%. Segregation analysis revealed the presence of two maximum likelihood solutions, one characterized a s a recessive Medelian gene and the other as a major effect with an am biguous transmission pattern. The presence of two such solutions is co nsistent with detection of two separate factors, each influencing the BMI distribution in a substantive manner. The evidence also supports a multifactorial background for BMI and suggests that the frequencies o f these two factors, one of which appears to be a gene, may vary among diverse populations in the United States.