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Assessment of gene-by-sex interaction effect on bone mineral density

Abstract: 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 expression quantitative trait loci (eQTL) analysis and bioinformatics network analysis. We conducted an autosomal genome-wide meta-analysis of gene-by-sex interaction on lumbar spine (LS) and femoral neck (FN) BMD in 25,353 individuals from 8 cohorts. In a second stage, we followed up the 12 top single-nucleotide polymorphisms (SNPs; p < 1 × 10(-5) ) in an additional set of 24,763 individuals. Gene-by-sex interaction and sex-specific effects were examined in these 12 SNPs. 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 and p = 3.0 × 10(-5) ; female effect = -0.007 and p = 3.3 × 10(-2) ), and 11 suggestive loci associated with either FN- or LS-BMD in discovery cohorts. However, there was no evidence for genome-wide significant (p < 5 × 10(-8) ) gene-by-sex interaction in the joint analysis of discovery and replication cohorts. Despite the large collaborative effort, no genome-wide significant evidence for gene-by-sex interaction was found to influence 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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral ResearchJournal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 2012, 27(10), 2039-2230

Editorial: John Wiley & Sons

 Año de publicación: 2012

Tipo de publicación: Artículo de Revista

 DOI: 10.1002/jbmr.1679

ISSN: 0884-0431,1523-4681

Autoría

LIU, CHING-TI

ESTRADA, KAROL

YERGES-ARMSTRONG, LAURA M.

AMIN, NAJAF

EVANGELOU, EVANGELOS

LI, GUO

MINSTER, RYAN L.

CARLESS, MELANIE A.

KAMMERER, CANDACE M.

OEI, LING

ZHOU, YANHUA

ALONSO, NEREA

DAILIANA, ZOE

ERIKSSON, JOEL

GARCÍA-GIRALT, NATALIA

GIROUX, SYLVIE

MARIA TERESA ZARRABEITIA CIMIANO