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  • Assessment of gene-by-sex interaction effect on bone mineral density
    Liu, Ching-Ti ...
    BACKGROUND: Sexual dimorphism in various bone phenotypes, including bone mineral density (BMD), is widely observed; however the extent to which genes explain these sex differences is unclear. To ... identify variants with different effects by sex, we examined gene-by-sex autosomal interactions genome-wide, and performed eQTL analysis and bioinformatics network analysis. METHODS: We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction onlumbar spine (LS-) and femoral neck (FN-) BMD, in 25,353 individuals from eight cohorts. In a second stage, we followed up the 12 top SNPs (P<1X10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. RESULTS:We detected one novel genome-wide significant interaction associated with LS-BMD at the Chr3p26.1-p25.1 locus, near the GRM7 gene (male effect=0.02 & p-valueŽ=3.0X10(-5) ; female effect=-0.007 & p-value=3.3X10(-2) ) and eleven suggestive loci associated with either FN-or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (P<5X10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. CONCLUSION: Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found influencing BMD variation in this screen of autosomal markers. If they exist, gene-by-sex interactions for BMD probably have weak effects, accounting for less than 0.08% of the variation in these traits per implicated SNP.
    Source: Journal of bone and mineral research. - ISSN 0884-0431 (Vol. 27, issue 10, 2012, str. 2051-2064)
    Type of material - article, component part
    Publish date - 2012
    Language - english
    COBISS.SI-ID - 3286641

    Link(s):

    http://onlinelibrary.wiley.com/doi/10.1002/jbmr.1679/pdf
    DOI

source: Journal of bone and mineral research. - ISSN 0884-0431 (Vol. 27, issue 10, 2012, str. 2051-2064)
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