Gene variants newly linked to osteoporosis, one is potential candidate for treatment drug target

A link between the loss of bone mineral density that can result in osteoporosis-related fractures and 153 new gene variants was found in a genome-wide association study of 142,487 individuals conducted by investigators at The University of Queensland and McGill University in Canada.

Individuals studied were from the UK Biobank and their bone mineral density (BMD) was obtained from quantitative ultrasounds of the heel. Findings showed there were 307 conditionally independent single-nucleotide polymorphisms (SNPs) that attained genome-wide significance at 203 loci, a result that researchers described as “explaining approximately 12% of the phenotypic variance.”

In addition, study co-authors and University of Queensland researchers John P. Kemp and David M. Evans found a strongly implicated gene, GPC6, which was not previously linked to osteoporosis.

Evans said in a press release, “What makes this gene particularly interesting is that it encodes a protein that is present on the surface of cells, making it a potential candidate for a drug target.”

There was increased bone thickness seen when investigators removed GPC6, a novel determinant of BMD, in studies using animal models, Evans noted.

Researchers also found several rare gene variants with large effect sizes.

They investigated the underlying cellular and molecular mechanisms of GPC6 and the new gene variants using bioinformatic, functional genomic annotation and human osteoblast expression studies; gene-function prediction; skeletal phenotyping of 120 knockout mice with deletions of genes adjacent to lead independent SNPs; and analysis of gene expression in mouse osteoblasts, osteocytes and osteoclasts. – by Susan M. Rapp

Disclosures: The authors report no relevant financial disclosures.

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Source:

Kemp JP, et al. Nat Genet. 2017.doi:10.1038/ng.3949. [Epub ahead of print]