SEGREGATION ANALYSIS OF FAT MASS AND FAT-FREE MASS WITH AGE-DEPENDENTAND SEX-DEPENDENT EFFECTS - THE STANISLAS FAMILY STUDY

Segregation analysis using a regressive model with age- and sex-depend ent effects was applied to family data of weight, fat mass (FM) and fa t-free mass (FFM) to investigate the major gene hypothesis. The sample consisted of 220 nuclear families from the 'Stanislas Cohort' who vol unteered for a free health examination (n = 913). FM and FFM were asse ssed by bioelectrical impedance. The data were adjusted for height and height(2) prior to analysis. The spouse, father-offspring, mother-off spring and sib-sib correlations were: 0.16, 0.18, 0.25 and 0.32 for we ight; 0.13, 0.20, 0.23 and 0.28 for FM; 0.18, 0.16, 0.29 and 0.41 for FFM. For the three phenotypes, models specifying a major gene with age - and sex-dependent effects and residual family correlations was bette r supported than models including only family correlations. For weight , the most parsimonious genetic model was a codominant model with a se x-dependent effect in parents and an age-increasing effect in offsprin g. For FM, the most parsimonious model was also a codominant model wit h sex-dependent effects in parents indicating higher effects in women than in men. For FFM, the most parsimonious model was a recessive mode l with no significant age or sex interaction, although the age interac tions paralleled those observed on weight in offspring. For weight and FM, mendelian transmission was rejected. For FFM, the Mendelian and t he environmental hypotheses were nearly equally supported and none was rejected when compared to general transmission. Then, evidence for a single major gene could not be inferred for any of the traits. This do es not preclude the existence of several genes acting in a more comple x way. However, our findings emphasize that weight is a composite phen otype reflecting different components which evolve in distinct ways du ring life span. For this reason, FM should be highly preferred to weig ht or BMI for the research of susceptibility genes to obesity. (C) 199 7 Wiley-Liss, Inc.