rs11606786 (LINC02763): linked to heel BMD

What the research says rs11606786, a variant in the genomic region of LINC02763 (a long intergenic non-coding RNA - a stretch of DNA that is transcribed into RNA but does not encode a protein), was identified as one of 1,362 independent SNPs (single nucleotide polymorphisms - single-letter changes in the DNA sequence) associated with estimated heel bone mineral density (eBMD) in a genome-wide association study of 394,929 individuals of European ancestry from the UK Biobank [Study 1]. The study clustered these SNPs into 899 genomic loci, of which 613 were newly reported at the time of publication [Study 1]. A polygenic risk score (a combined score derived from thousands of such variants) built from 22,886 SNPs showed a correlation of 0.415 with heel BMD, rising to 0.496 when combined with height, weight, age, and sex [Study 1].

Reported associations

• Estimated heel bone mineral density (eBMD): rs11606786 is among variants reaching genome-wide significance (p < 6.6 × 10^-9) for association with heel bone mineral density, measured non-invasively by quantitative ultrasound of the heel bone [Study 1]
• Osteoporosis risk (polygenic context): In the study's multi-SNP risk score framework - which incorporates this variant among thousands - individuals in the lowest-scoring 2.2% showed a 17.4-fold increase in osteoporosis risk and a T-score reduction of 1.16 units relative to the average [Study 1]
• Fracture risk (polygenic context): The same lowest-scoring group showed a 1.87-fold increase in risk of bone fracture [Study 1]

Evidence quality The association derives from a large, well-powered genome-wide association study of 394,929 European-ancestry participants, applying a strict genome-wide significance threshold of p < 6.6 × 10^-9 [Study 1]. The study's genomic inflation factor (λGC = 1.59) and linkage disequilibrium score regression intercept (1.21) suggest that most of the statistical signal reflects genuine polygenicity rather than population stratification artifacts [Study 1]. Important caveats: the provided study text does not report the individual effect size or p-value for rs11606786 specifically - those are in the study's supplemental table (S1 Table) referenced but not reproduced here. The osteoporosis and fracture risk figures described above reflect the aggregate bottom 2.2% of a 22,886-SNP polygenic score, not the isolated effect of rs11606786 alone. The cohort was restricted to European ancestry, limiting generalizability to other populations. No independent replication results for this specific variant are described in the provided text, and the preliminary, discovery-phase nature of many of the 613 newly reported loci should be noted.

Study sources

1. Unknown authors, Unknown journal - Identification of 613 new loci associated with heel bone mineral density and a polygenic risk score for bone mineral density, osteoporosis and fracture