Human genetics of osteoporosis

A family history of hip fracture carries a twofold increased risk of fracture among descendants. Genetic factors indeed play a major role in the determination of bone mineral density (BMD) and osteoporosis risk. Multiple chromosomal loci have been mapped by linkage approaches which potentially carry hundreds of genes involved in the determination of bone mass and quality. Association studies based on candidate gene polymorphisms and subsequent meta-analyses, and the more recent genome-wide association studies (GWAS), have clearly identified a handful of genes associated with BMD and/or fragility fractures. Among them are genes coding for the LDL-receptor related protein 5 (LRP5), estrogen receptor alpha (ESR1) and osteoprotegerin, OPG (TNFRSf11b). However, the percentage of osteoporosis risk explained by any of these polymorphisms is small, indicating that most genetic risk factors remain to be discovered and/or that interaction with environmental factors needs further consideration.

Key words: bone, osteoporosis, gene, polymorphism, fracture, LRP5, interleukin-6, estrogen receptor, vitamin D receptor, osteoprotegerin, QTL, GWAS