Genetic Variants in Adult Bone Mineral Density and Fracture Risk Genes are Associated with the Rate of Bone Mineral Density Acquisition in Adolescence

Nicole M Warrington, John P Kemp, Kate Tilling, Jonathan H Tobias, David M Evans

Research output: Contribution to journalArticle (Academic Journal)peer-review

18 Citations (Scopus)

Abstract

BACKGROUND: Previous studies have identified 63 single nucleotide polymorphisms (SNPs) associated with bone mineral density (BMD) in adults. These SNPs are thought to reflect variants that influence bone maintenance and/or loss in adults. It is unclear whether they affect the rate of bone acquisition during adolescence.

METHODS: Bone measurements and genetic data were available on 6,397 individuals from the Avon Longitudinal Study of Parents and Children at up to five follow-up clinics. Linear mixed effects models with smoothing splines were used for longitudinal modelling of BMD and its components bone mineral content (BMC) and bone area (BA), from nine to 17 years. Genotype data from the 63 adult BMD associated SNPs were investigated individually and as a genetic risk score in the longitudinal model.

RESULTS: Each additional BMD lowering allele of the genetic risk score was associated with lower BMD at age 13 (per allele effect size, 0.002g/cm(2) [SE=0.0001, P=1.24x10(-38)]) and decreased BMD acquisition from nine to 17 years (P=9.17x10(-7)). This association was driven by changes in BMC rather than BA. The genetic risk score explained approximately 2% of the variation in BMD at nine and 17 years, a third of that explained in adults (6%).

CONCLUSION: Genetic variants that putatively affect bone maintenance and/or loss in adults appear to have a small influence on the rate of bone acquisition through adolescence.

Original languageEnglish
JournalHuman Molecular Genetics
DOIs
Publication statusPublished - 4 May 2015

Bibliographical note

© The Author 2015. Published by Oxford University Press.

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