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SMOC1 and CLDN14: novel genes associated with bone mineral density
DOI:10.1038/bonekey.2014.113
Data from 27 061 subjects within multiple genome-wide association studies (GWAS) were reviewed in a three-stage meta-analysis to clarify the genetic determinants of bone mineral density (BMD).
Seven GWAS with 11 140 participants were reviewed in Stage 1. The 33 single nucleotide polymorphisms (SNPs) identified were then subjected to in silico replication in Stage 2, which included 9258 samples. The three most promising SNPs were independently validated in Stage 3 in 6663 further subjects.
Thirteen genes already associated with BMD had their association independently confirmed. The study also highlighted two novel genes with a potential impact on BMD; SMOC1 on chromosome 14 and CLDN14 on chromosome 21. In vivo expression studies in osteoclastogenic cell precursors from menopausal women with high/low hip BMD revealed that both genes were expressed differentially (P<0.05). SMOC1 (secreted modular calcium binding protein 1) is known to play a part in regulating bone development while CLDN14 (claudin 14), an integral membrane protein that helps form tight junction strands, may have a role in regulating calcium metabolism.
Editor’s comment: The two candidate genes identified by this study are not completely novel in relation to bone metabolism. SMOC1 variants have been associated with digit length ratio, while CLDN14 variants have been linked with development of kidney stones and reduced hip BMD in a study population that included people from Iceland and The Netherlands.
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