deCODE Discovers Genetic Variants Influencing Bone Mineral Density
A team of scientists from deCODE genetics and academic colleagues from Iceland, Denmark and Australia report the discovery of five single letter variants (SNPs) at five different sites in the human genome that impact bone mineral density (BMD) and predispose to fracturing of bones. BMD is a principal measure of the presence and severity of osteoporosis, a common, progressive and often debilitating condition in which bones become thinner and more prone to fracture, even from minor falls or blows. As an accompanying editorial in the NEJM points out, although BMD has long been known to have a significant inherited component, these are the first validated and replicated genetic variants ever linked to BMD through a genome-wide scan of SNPs.
The findings demonstrate that the genetic component of BMD appears to involve many genetic variants each conferring relatively modest increases in risk, but that such variants can be found using studies of sufficient size and power. In this study, the deCODE team analyzed more than 300,000 SNPs across the genomes of some 10,000 Icelandic participants, mainly women, and replicated its findings in cohorts of approximately 4000 Danish and Australian, again mainly female, participants.
The SNPs associated with BMD are located on chromosomes 1p36, 6q25, 6p21, 8q24, and 13q24. Three of these loci are located near genes known to be involved in bone mineral density, and one, 13q14, is close to a gene known as RANKL which is already being used as target for drug development by a major pharmaceutical company. Although these variants confer an increase in risk that is in the range of 5-15% compared to non-carriers of the variants, they are all quite common and so may account for a sizable proportion of the inherited component of low BMD.
"These findings show yet again the power of large-scale studies for adding to our understanding of complex conditions. These variants alone do not confer individual risk sufficient for making a diagnostic test with clinical value, though we are only getting started in this search, and these variants will be the third recent update to the profiles of subscribers to our deCODEme service. In practical terms, these discoveries provide new insight into certain biological pathways known to be involved in BMD and osteoporosis -- such as that on chromosome 13 -- and alerting us to new pathways that should be investigated. This information can inform future drug discovery, or indeed help to target therapies now in development to those individuals who may benefit from medicines aimed at particular pathways," said Kari Stefansson, CEO of deCODE.