Segregation analysis of height‐adjusted weight with generation‐ and age‐dependent effects: The Nancy family study

Abstract

A segregation analysis using a regressive model with generation- and age-dependent effects was applied to familial data of height-adjusted weight to investigate the major gene hypothesis. The sample included 629 nuclear families with 2,534 members volunteering for a free health check-up in the Preventive Medicine Center of Vandoeuvre-lès-Nancy, France. The familial correlations were 0.094 +/- 0.040 between spouses, 0.198 +/- 0.023 between parent and offspring, and 0.327 +/- 0.034 between siblings. The variability of the trait was higher in parents than in offspring. The most parsimonious genetic model indicated a codominant major effect increasing with age in childhood, then stabilizing in adulthood. The same data were analyzed using the classical mixed model, assuming equality of variances between parents and offspring, no resemblance between spouses, similar parent-offspring and sib-sib correlations, and identical effects in parents and offspring. This analysis indicated a recessive solution. In both analyses, mendelian transmission was rejected. However, the mixture of two distributions in the recessive model, instead of three in the codominant one, was less constraining with respect to the test of transmission probabilities, and the rejection of mendelian transmission was due to a single family in the recessive case, instead of several families in the codominant one. This could possibly explain why previous studies, all using the mixed model, found evidence for a recessive major gene. Although the major gene hypothesis cannot be definitely ruled out from our results, the mechanism appears more complex than the effect of one single gene.

Segregation analysis of fat mass and fat-free mass with age- and sex-dependent effects: The Stanislas family study

“…est correlations observed between sibs. The correlations estimated for height-adjusted weight were very close to those observed in our earlier study [Tiret et al, 1992]. Table IV summarizes the results of segregation analyses carried out on the three traits.…”

“…Analyses were performed successively on weight, FM, and FFM. In order to compare the results of the present analyses with those of our earlier paper [Tiret et al, 1992], all traits were adjusted on height and height 2 before analysis, separately in fathers, mothers, sons, and daughters. The height-adjusted weight was then strictly comparable to the trait analyzed in our earlier paper [Tiret et al, 1992].…”

“…While all studies found evidence for commingling in the distribution of BMI, some of them supported the hypothesis of transmission of a major gene Moll et al, 1991;Borecki et al, 1993] while others did not [Rice et al, 1993a;Tiret et al, 1992]. This discrepancy might be explained by the fact that BMI is an indicator of heaviness rather than fatness, which reflects different weight components, including fat mass (FM) and fat free-mass (FFM).…”

“…As part of this study, FM and FFM were assessed by bioelectrical impedance in a sample of 220 nuclear families. These families had the same characteristics as those included in our previous segregation analysis of height-adjusted weight [Tiret et al, 1992]. This analysis suggested the existence of a major factor with effects increasing with age in offspring, but whose transmission patterns did not conform to the mendelian hypothesis.…”

Familial Aggregation of Morbid Obesity

“…demonstrated that weight gain, fat distribution, and body-mass index are significantly affected by genetic influences (5,23). In addition to the twin studies, investigations involving the segregation analysis of randomly ascertained family data have suggested recessive major gene transmission for body mass index (18,24,2S) or possibly codominant transmission (31). However, even the genetic causes of obesity are likely heterogeneous and may respond differently to various environmental stimuli.…”