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lüll Genetics of osteoporosis Ralston SH; Uitterlinden AGEndocr Rev 2010[Oct]; 31 (5): 629-62Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass, defects in the microarchitecture of bone tissue, and an increased risk of fragility fractures. Twin and family studies have shown high heritability of bone mineral density (BMD) and other determinants of fracture risk such as ultrasound properties of bone, skeletal geometry, and bone turnover. Osteoporotic fractures also have a heritable component, but this reduces with age as environmental factors such as risk of falling come into play. Susceptibility to osteoporosis is governed by many different genetic variants and their interaction with environmental factors such as diet and exercise. Notable successes in identification of genes that regulate BMD have come from the study of rare Mendelian bone diseases characterized by major abnormalities of bone mass where variants of large effect size are operative. Genome-wide association studies have also identified common genetic variants of small effect size that contribute to regulation of BMD and fracture risk in the general population. In many cases, the loci and genes identified by these studies had not previously been suspected to play a role in bone metabolism. Although there has been extensive progress in identifying the genes and loci that contribute to the regulation of BMD and fracture over the past 15 yr, most of the genetic variants that regulate these phenotypes remain to be discovered.|Animals[MESH]|Chromosome Mapping[MESH]|Genetic Predisposition to Disease[MESH]|Genome-Wide Association Study[MESH]|Humans[MESH]|Osteoporosis/*genetics/metabolism[MESH]|Quantitative Trait Loci[MESH] |