The effect of depression status on osteoarthritis: A powerful two-step Mendelian randomization study

Osteoarthritis (OA) is a common degenerative disease that affects millions of individuals worldwide.

There is no conclusive epidemiological evidence regarding the relationship between OA, depression, and whole-body fat mass. In this study, we conducted a two-step Mendelian randomization analysis to determine the causal relationships between them.

The published summary-level data are from genome-wide association studies (GWAS). Our study included 357,957 samples and 10,828,862 SNPs. Finally, the outcome GWAS data for OA came from a GWAS on the genetic architecture of OA using UK Biobank data. This study included 50,508 samples and 15,845,511 SNPs. We used five different modes of analysis, including inverse variance weighted meta-analysis (IVW), MR-Egger regression, weighted median, simple mode, and weighted mode, to explore causal relationships.

We found a positive correlation between depression and body fat mass, with depression leading to body fat mass an increase in (IVW result: p = 3.39E-07, OR (95 % CI) =2.16 (1.61, 2.90)). We also found a positive correlation between body fat mass and OA, with body fat mass increasing the risk of OA (IVW result: p = 1.65E-33, OR (95 % CI) = 1.98 (1.77, 2.21). Body fat mass played an important role as a mediator in the causal relationship between depression and OA, with approximately 14 % of the risk of OA caused by depression being mediated by body fat mass.

Our study offers reliable evidence that depression has a detrimental impact on the risk of OA. Future research can support these associations from improving depressed effect, including social, biological, and behavioral factors, to reduce the risk of chronic diseases such as osteoarthritis. And we identified high-risk variation of alleles which associated with OA and depression can be used to predict disease and provide a basis for clinical intervention and treatment of OA.