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Mitchell et al. Bone density in children and genetic loci for adult bone fragility
DOI:10.1038/bonekey.2016.28
A total of 63 bone mineral density (BMD) loci identified in adults were used to calculate genetic risk scores to investigate if the loci were associated with BMD trajectory during childhood.
Mitchell et al. analyzed longitudinal data from the BMD in Childhood Study to obtain Z-scores for the spine, total hip and femoral neck and for total body (less head) bone mineral content. During this study, the 798 participants, all of European ancestry and with a male:female ratio of 54:46, received up to 6 annual DEXA scans.
Lower Z-scores were found to be associated with GRS for adult fracture and WNT signaling. The overall adult GRS showed the strongest correlation with lower Z-scores in female children (P-interaction ⩽0.05 for all body sites). Splitting out the individual GRS, WNT GRS associations for all sites were consistent across all ages and for males and females while mesenchymal stem cell GRS correlated with lower Z scores for both sexes at the femoral neck and total hip. Female children of all ages showed a higher correlation between Z scores at all sites and the RANK-RANKL-OPG GRS.
Editor’s comment: A unique contribution of this study is that the authors tested for sex interactions with each genetic risk score. This approach suggests that genetic loci involved in fracture risk later in life, are already important in children, particularly girls, as they impact on bone formation during a crucial stage of adolescent development.
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