The Contribution of Genes to Osteoarthritis

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Osteoarthritis (OA) is the most prevalent form of arthritis in the elderly. A large body of evidence, including familial aggregation and classic twin studies, indicates that primary OA has a strong hereditary component that is likely polygenic in nature. Furthermore, traits related to OA, such as longitudinal changes in cartilage volume and progression of radiographic features, are also under genetic control. In recent years, several linkage analysis and candidate gene studies have been performed and have unveiled some of the specific genes involved in disease risk, such as FRZB and GDF5. The authors discuss the impact that future genome-wide association scans can have on our understanding of the pathogenesis of OA and on identifying individuals at high risk for developing severe OA.

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Familial aggregation

The risk ratio for a relative of an affected individual, compared with the population prevalence, is a measure for familial aggregation of complex diseases [10]. It has been applied extensively in the field of genetic epidemiology to derive the statistical power available for a given condition to detect genetic linkage to a complex genetic disorder [11]. For affected sib-pairs, this sib recurrence risk is termed the lambda sib (λs). Table 1 shows estimates of the sibling recurrence risk for

Classic twin studies

The classic twin study compares resemblances between identical or monozygotic (MZ) and nonidentical or dizygotic (DZ) twins. MZ twins derive from a single fertilized egg and therefore inherit identical genetic material, unlike DZ twins, who, on average, share only 50% of their genetic material. Comparing the resemblance of MZ twins for a trait or disease with the resemblance of DZ twins offers the first estimate of the extent to which genetic variation determines variation of that trait. If MZ

Linkage analyses

In genetics, a locus refers to a particular location on a chromosome or the DNA at that position. It can be present in the population in one or more forms, called alleles. If more than one allele exists for a locus, it is termed polymorphic. When the specific alleles at two or more loci in the same chromosome are being studied, the particular combination of alleles is called a haplotype. A polymorphic locus genotyped solely because its inheritance can be monitored, and not because it may be

Genetic associations

Genetic association studies provide a means of quantifying the effects of specific gene variants on disease occurrence. It is important to distinguish between a genetic association and the role of a gene or its encoded product in disease. For example, matrix metalloproteases (MMPs) are of key importance in OA, yet genetic variants in these genes have not been reported to be associated with susceptibility to disease, which can be explained if over- or underexpression of the gene encoding MMPs

What can we expect in the years to come in genetic research in osteoarthritis?

Genome-wide association studies (GWAS) are a result of the human genome and HapMap projects (http://www.hapmap.org) and, if successful, can find variants in specific genes, or narrow genomic regions, that are associated with the presence or severity of a specific clinical condition. The information conveyed by these studies is unlikely to influence clinical practice in the immediate future, yet it represents an important advance in medicine [73]. The GWAS approach enables a genome-wide

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    This work was supported by EC framework 7 programme grant 200800 TREAT-OA and by Arthritis and Research Campaign project grant 17716.

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