Osteoarthritis (OA) is known to have an important genetic component and human genetic studies can help unravel the molecular mechanisms responsible for joint damage and nociception involved in OA. Genetic studies in humans have identified molecules involved in signaling cascades that are important for the pathology of the joint components such as the bone morphogenetic protein growth differentiation factor 5 (GDF5). Genomewide association scans (GWAS) in Asians have uncovered a likely role for structural extracellular matrix components (DVWA), and for molecules involved in immune response (HLA class II DQB1 and BTNL2) but these genes are not associated in Caucasian patients. In Caucasians a ~300 kilobase region in chromosome 7q22 containing several genes has been found to be reproducibly associated with OA. A recent European GWAS taking advantage of imputation techniques has uncovered a variant in the MCF2L gene as significantly associated with large joint OA. MCF2L is involved in neurotrophin mediated regulation of cell motility in the peripheral nervous system, and thus potentially implicated in nociception in OA. As the number of OA cases with genomewide genotyping increases it is expected that many more reproducible variants implicated in OA will be reported. This article is part of a Special Issue entitled "Osteoarthritis".
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