Translational genetics of osteoporosis : from population association to individualized prognosis

Genetic factors have been found to play an important role in osteoporosis and fracture risk. Initial studies of monozygotic (identical) and dizygotic (nonidentical) twins and subsequently family studies demonstrated a high heritability, up to 60-80% of various measures of bone structure and a clear, albeit modest, heritability of fracture risk. The demonstration of high heritability has led to a large body of studies aimed at identifying the genes responsible. The types of studies can be broadly divided into a candidate gene approach or genome-wide search strategy using either linkage or association studies. The candidate gene approach involves directly testing variation in genes known to be involved in bone biology for their role in osteoporosis and fracture risk. The genomewide search strategy involves systematically screening all genes using DNA markers uniformly distributed throughout the entire genome. Localization is then progressively refi ned until a gene can be identified. Association studies are either population-based or case-control studies relating a polymorphism of a certain candidate gene to the desired phenotype. Association studies are also suitable for a genome-wide analysis where identified SNPs (single-nucleotide polymorphisms) are in linkage disequilibrium with the phenotype studied. Linkage studies relate the inheritance of genetic markers to the inheritance of phenotypes within families.