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• W2497602302 abstract "So-called “complex” diseases include the typical common age-related disorders such as cancer, cardiovascular disease, and diabetes, but also the major diseases of the locomotor system, that is, osteoarthritis and osteoporosis, Epidemiological research of these complex diseases has identified anthropometric, behavioral, and serum parameters as risk-factors for incidence and progression of the disease. However, over the past decade genetic (deoxyribonucleic acid (DNA)) polymorphisms have gained considerable interest in this respect, propelled by the revolutionary developments sprouting from the Human Genome Project and its sequelae that have identified most human genes and uncovered a plethora of polymorphic DNA variants, embodying part of the genetic risk factors for these complex diseases. By now literally tens of genetic factors for osteoporosis have been discovered, but progress in identifying genetic factors has been hampered in the past by often variable results in candidate gene studies. Because of the multifactorial genetic architecture of the diseases and the small effect size for each individual risk polymorphism, this is mostly due to low statistical power and limitations of analytical methods. Hypothesis-free genome-wide scanning approaches were early on proposed to find the responsible genes. Linkage analysis in exotic rare pedigrees has been very successful to identify rare mutations in bone genes with severe effects, and unveil new bone biology pathways. Genome-wide association studies (GWAS) have proven very successful to identify tens of common variants explaining population variation in, for example, bone mineral density, and to identify novel bone genes and pathways. Next generation sequencing is now used to again identify mutations in bone genes in families (but faster), and is also applied in large populations to study the contribution of rare variants to explain the genetics of bone traits. To identify genetic markers for osteoporosis a large (global) collaborative consortium, called GEnetic Factors for OSteoporosis (GEFOS), was established, that uses standardized methodology and definitions, to quantify by meta-analysis the often subtle effects of the responsible gene variants. Such genetic insights will be useful in understanding bone biology and are likely to find applications in clinical practice. In this chapter we will review the different approaches to identify and study genetic risk factors for osteoporosis and present some of the results obtained so far in the quest for osteoporosis genes and their implications in a clinical setting." @default.
• W2497602302 created "2016-08-23" @default.
• W2497602302 creator A5021938845 @default.
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• W2497602302 creator A5067726769 @default.
• W2497602302 date "2013-01-01" @default.
• W2497602302 modified "2023-10-08" @default.
• W2497602302 title "Genetic Determinants of Osteoporosis" @default.
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