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Genetic Variation in Female BMI Increases with Number of Children Born but Failure to Replicate Association between GNβ3 Variants and Increased BMI in Parous Females

Published online by Cambridge University Press:  21 February 2012

Belinda K. Cornes*
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia; School of Medicine, Central Clinical Division, University of Queensland, Brisbane, Queensland, Australia. belinda.cornes@gmail.com
Sarah E. Medland
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia; Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, United States of America.
Penelope A. Lind
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Dale R. Nyholt
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Grant W. Montgomery
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Nicholas G. Martin
Affiliation:
Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
*
*Address for correspondence: Belinda K. Cornes, Genetic Epidemiology, Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, QLD, 4029, Australia.

Abstract

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Objective: As post-pregnancy weight retention in women is a risk factor for obesity later in life, we assessed the changes in magnitude of genetic and environmental variation in BMI due to parity in an Australian female sample, comprising 11,915 female twins and their sisters. Results: Total variance of BMI increased with parity, primarily driven by an increase in nonadditive genetic variance. This finding was of particular interest given Gutersohn et al's (2000) report of recessive association between post-partum weight retention and the 825T allele of the GNβ3 gene (rs5443) at 12p13.31. Hence, we attempted to replicate this association and test an additional three SNPs also located near or on GNβ3 (rs10744716 (upstream), rs5442 (exon 10), rs5446 (exon 11)) in a sample of 3131 females and 1693 males from 2585 twin families. No association was found between these SNPs among females, even when allowing for a genotype by parity effect. However, a significant association was observed among males for rs10744716 (χ22 = 10.22, p = 0.006; effect size = 0.47kg/m2), representing a novel association between a region upstream of GNβ3 and male BMI.

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Articles
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Copyright © Cambridge University Press 2009