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

Segregation analysis of height‐adjusted weight with generation‐ and age‐dependent effects: The... 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. © 1992 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Genetic Epidemiology Wiley

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

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References (48)

Publisher
Wiley
Copyright
Copyright © 1992 Wiley‐Liss, Inc., A Wiley Company
ISSN
0741-0395
eISSN
1098-2272
DOI
10.1002/gepi.1370090603
pmid
1487137
Publisher site
See Article on Publisher Site

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. © 1992 Wiley‐Liss, Inc.

Journal

Genetic Epidemiology – Wiley

Published: Jan 1, 1992

Keywords: regressive model; familial resemblance; body mass index

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