Wednesday, April 30, 2008

Risk Alleles for Osteoporosis Identified

The latest issue of The Lancet has this interesting article on a genome-wide association study for osteoporosis and osteoporotic fracture. Here is a sample:

Osteoporosis and its main complication, fragility fractures, incur substantial global morbidity and mortality.1 The public-health burden of this disease is US$17 billion every year in direct expenditure—and this is expected to increase dramatically as populations age.2 Osteoporosis is defined clinically through the measurement of bone mineral density, which remains the single best predictor of primary osteoporotic fractures.3 Bone mineral density is highly heritable, with estimates from a cohort study in the UK of 78% heritability of density at lumbar spine and 84% at femoral neck;4 these figures are consistent with other twin studies.5 Only a few well-replicated studies of candidate genes for osteoporosis have so far emerged,6–8 suggesting that bone mineral density is a complex polygenic trait.5

Genome-wide association studies have been facilitated by the HapMap project, and by recent advances in genome-wide genotyping arrays that provide a high degree of genome coverage.9 We therefore undertook a genome-wide association study to identify genetic loci that influence bone mineral density.

....We have identified genetic variants that decrease bone mineral density and predispose people to osteoporosis and osteoporotic fracture. The increased risk of osteoporotic fracture in people who had both risk alleles was independent of the effect of these alleles on bone mineral density.

....In conclusion, the risk alleles we have identified justifiy further clinical and biological investigations. These SNPs alone are unlikely to change current clinical practice, but as has been shown for other diseases,59 extended panels of several SNP markers could be used in the future, in addition to traditional risk factors, to better identify populations who are at high risk for osteoporotic fractures.