The main pathological manifestations of osteoarthritis are changes in cartilage, generation of bone redundancy, and inflammation of synovial membrane etc.[17-19] , with the aging of the population and the rising obesity rate globally, it has brought about a very great impact on the quality of life of the majority of middle-aged and elderly people[20] , which not only becomes a shackle to the happiness of the elderly life, but also brings about an impact on the health care security and social security[9] . Depression, as a common mental disorder, has also been high in incidence. This MR study investigates the causal relationship between depression and osteoarthritis. Unlike previous clinical studies that collected samples, we obtained the relevant information from a database to conduct the MR study, which not only avoids the influence of interfering factors on the accuracy of the results, but also obtains results that are even better than those obtained from a randomised controlled trial of cases and controls. This study is also the first to investigate the correlation between depression and osteoarthritis, and the most intuitive conclusion from the results of the study is that there is a causal association between depression and osteoarthritis, and that depression is a risk factor for osteoarthritis.
Regarding the association between depression and osteoarthritis, previous clinical studies have shown that the effects of depression on osteoarthritis are mainly reflected in the negative impact on pain and deterioration. Patients with depression combined with osteoarthritis have more pronounced impaired mobility, faster disease progression, and stronger pain compared to patients with osteoarthritis alone[21] . The correlation can be elaborated in the following aspects: ① The pain symptoms of osteoarthritis are mainly joint pain, but studies have shown that non-inflammatory pain brought by depression such as neurofibromyalgia[22] neuropathic pain can also stimulate osteoarthritis and bring serious negative effects on its pain symptoms. ② The development of osteoarthritis is closely related to a variety of inflammatory factors, such as interleukin-1, interleukin-6, and tumour necrosis factor[23-25] . The induction of multiple inflammatory factors not only negatively affects osteochondral cartilage, but some inflammatory factors, especially interleukin-1, stimulate the production and delivery of other inflammatory factors such as interleukin-8[26] . Previous studies have shown that depression is also a disease related to chronic inflammation. In the course of depression, there is a significant increase in inflammatory factors such as interleukin, tumour necrosis factor and C-reactive protein[27] , of which the increase in interleukin 6 is associated with a decrease in serotonin metabolites, and a decrease in serotonin metabolites is an important factor in the production of depression[28] . Overseas studies have also shown that patients suffering from long-term inflammatory diseases are more prone to depression than the general population. Patients with long-term inflammatory diseases are more prone to depression than general patients. (3) In patients suffering from arthritis, most of the patients, although arthritis will not affect the life expectancy, but suffers from long-term pain, seriously affecting the quality of life[29-30] , coupled with persistent monetary costs and continuous medication, patients will develop anxiety and boredom over time, to the already depressed patients is even worse, seriously destroying the physical and mental health of patients with depression and arthritis co-morbidities. ④ Long-term depressed patients have significantly lower sleep quality[31] , the decline in sleep quality by affecting the inflammatory cell pathway and increase sympathetic nerve tone and so on, contributing to the occurrence of high blood pressure, heart disease and other diseases[32-33] , and cardiovascular disease is one of the important causes of osteoarthritis[34] .
Of course, there are some limitations in this study, because the sample base used for the analysis is from the GWAS database, and there is no way to explore the basic physical condition of each sample, which can not completely exclude the individualised differences, and may lead to a certain degree of bias, but based on the analysis of a large sample of data, the unavoidable variability has been reduced to a minimum; the study shows that there is a correlation between depression and osteoarthritis, but its Although the association between depression and osteoarthritis has been demonstrated, further clinical observation and practice are needed to establish specific prevention and treatment options; the present study was limited to the European population, and it cannot be claimed that it is applicable to all races, and experiments should continue to be carried out to investigate the suitability and effectiveness of the treatment for all populations around the world.
Overall, Mendelian randomisation analysis is a powerful tool for studying disease associations, and the results of the present study reveal a causal association between depression and osteoarthritis and that depression is a risk factor for osteoarthritis. These depressed groups suffer from psychiatric factors, and osteoarthritis as a complication would be a quick knife to the throat of the depressed patients. This study provides a potential basis for the development of osteoarthritis due to depression, provides new ideas and research support for the prevention and treatment of osteoarthritis in the future, and opens the door for future research on the association between psychiatric disorders and osteoarthritis.