Genetics and Osteoarthritis

Osteoarthritis (OA) is a degenerative disease of the joints that has complex pathogenesis because of the many factors that lead to cartilage deterioration. OA is the most common form of arthritis and is one of the significant causes of disability. Around 80% of people over the age of 65 years of age have radiographic indications of OA. A major percentage of these individuals require medical intervention due to limited daily living activities. Researchers now believe that specific forms of OA have a strong genetic component.

Experts recently found that the genetic basis of OA does not follow what is known as a typical Mendelian inheritance pattern, but rather it is due to alterations of multiple genes. The complex nature of OA is evident with the identification of a high number of candidate genes. Researchers have found that several genes are altered in subjects with OA, and that inheritance is a significant consideration in the diagnosis and treatment of this condition.

Disease experts once criticized genetic research regarding OA. Now, however, research studies reveal that OA has an intriguing genetic component, and experts are optimistic that this could lead to better treatment modalities, earlier detection, and enhanced measures of prevention.

The First Genetics Study

Stechner first studied genetics associated with OA in 1941. He demonstrated that the existence of Heberden nodules (joint swelling) of the fingers were three times more likely to occur in twins when compared to the general population. His findings showed that these lesions were inherited autosomal dominant factors and more prevalent in women.

Multiple Gene Factors and the Polygenic Inheritance Theory

Many studies support a polygenic inheritance theory, as opposed to a defect in one gene. Researchers believe that multiple gene factors influence the progression and severity of OA, and they estimate that there is approximately a 50% genetic influence. Some epidemiological studies report a 40% probability of inheritability for OA of the knee and around a 65% probability of inheritability for OA of the hips and hands. These predictions are based on identification of specific OA-related genetic sequences on specific parts of chromosomes, supporting a “common variants-multiple disease” hypothesis.

Susceptibility of Developing Osteoarthritis

There are certain ways in which to identify genes (lengths of DNA) that relate to the complex pathology of OA. One involves the genome wide linkage scan and the evaluation of candidate genes. With this expensive procedure, there is genotyping of various polymorphic (genetic variant) markers from several affected people belonging to the same family. Researchers have been able to detect relationships between 12 chromosomes using this technique, making the complexity of OA transmission evident. Five different OA-related genetic sequences on specific parts of chromosomes (known as loci) were detected when chromosomal analysis was carried out, leading researchers to propose that these chromosomes are carrying the ‘risk’ for osteoarthritis.

Genes that Code for Collagen

The genes that are involved in the coding for structural proteins of cartilage extracellular matrix also play a role in the OA development process. The main one of interest is collagen type II gene (COL2A1). Experts believe that alterations in this particular gene lead to the degeneration of joints seen in osteoarthritis. Other significant OA genes include COL9A2, COL11A1, COL11A2, and COMP (cartilage oligomeric matrix protein gene). In 2005, researchers found that specific mutations in the COL1A1 gene were actually linked with a lower chance of hip OA in women.

The Role of Cell Signaling Molecules (Cytokines)

Recent research reports show that the inflammatory process is important for the pathology of OA. While OA is not an autoimmune condition, there are various cytokines (cell signaling molecules) involved in cartilage metabolism and the production of synovial cells and cartilage cells.

Interleukin 1 (IL-1) is an important cytokine that produces special enzymes capable of breaking down cartilage. If cytokines remain in harmony at the joint, cartilage remains intact. If however, cytokines release too many enzymes, then the cartilage can degenerate. Researchers therefore suggest that various genes coding for key interleukins play a role in the genetic susceptibility to OA.

The Role of Chondrocytes

Recently, investigators found a particular role for genes in endochondral ossification, an important process that occurs with early skeletal development. One hypothesis suggests that early skeletal development that is ‘under par’ increases the risk of OA in middle age. Other experts suggest that genetic variants contribute to changes in chondrocytes (cartilage cells) later on in life, and there is also evidence confirming the role of chondrocytes in cartilage degradation. This means that researchers are now focusing on chondrocyte differentiation during early skeletal development.

Other Genes in the Osteoarthritic Process

Genetic investigators discovered several significant genes associated with OA development and progression. Alterations in the estrogen receptor a gene (ERa) affects the structure and function of tissues associated with OA progression. Recent epidemiological studies on women found that the loss of estrogen is directly associated with hip and knee OA development. Vitamin D and its receptor, VDR, also are significant in bone metabolism and OA, helping regulate calcium metabolism and cellular function. Another gene that is specific to bone formation is the Frizzled Related Protein gene (FRZB), and mutations of this gene are directly associated with OA progression.

Other Genetic Conditions and Osteoarthritis

There are many inherited conditions characterized by the early onset of OA. Some families have chondrodysplasia, a mild inherited cartilage disorder probably linked with the development of OA. People with the genetic condition multiple epiphyseal dysplasia (MED) have irregular ossification of the epiphyses (the long bone end at the joint) and early onset OA, particularly in the large, weight-bearing joints. Researchers found that mutations of specific genes existed in individuals with MED and OA.


OA is a complex disease that has a strong genetic component. Whilst several genetic mechanisms remain a mystery, it is evident that there are patterns of different genetic expressions in those suffering osteoarthritis, when compared with those who do not. Advances in scientific research during the last decade now allow us hope that the tools for prevention of and early detection of OA will be available soon.


  • Fernandez-Moreno, M., Rego, I., Carreira-Garcia, V., & Blanco, F.J. (2008). Genetics in osteoarthritis. Current Genomics, 9(8), 542-547. doi: 10.2174/138920208786847953
  • Newman, B. & Wallis, G.A. (2002). Is osteoarthritis a genetic disease? Clinical Investigative Medicine, 25(4), 139-149.
  • Shiro, I. (2007). New gene associations in osteoarthritis: What do they provide, and where are we going? Current Opinion in Rheumatology, 19(5), 429-434, doi: 10.1097/BOR.)b013e32825b079d

Last reviewed 26/Feb/2014


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Dr Merlin Thomas

Professor Merlin Thomas is Professor of Medicine at Melbourne’s Monash University, based in the Department of Diabetes. He is both a physician and a scientist. Merlin has a broader interest in all aspects of preventive medicine and ageing. He has published over 270 articles in many of the worlds’ leading medical journals

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