Genetic variation in female BMI increases with number of children born but failure to replicate association between GNbeta3 variants and increased BMI in parous females.

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. [ABSTRACT FROM AUTHOR]