Arthritis, including osteoarthritis (OAR) and rheumatoid arthritis (RAR), affects millions, causing joint pain and damage. OAR causes deterioration of cartilage and bones, affecting more than 500 million people with pain and walking difficulties. RAR is an autoimmune disease that leads to joint inflammation and muscular pains, affecting about one percent of the population with enhanced probabilities for severe infections and heart diseases. Lifestyle factors such as smoking, alcohol, and coffee intake are linked to arthritis, but ethical constraints limit research. Mendelian Randomization (MER) techique overcomes these limitations by using genetic variants to study these links. However, varying qualities and results in MER studies call for more comprehensive research to clarify these associations.
In the present study, researchers conducted a MER analysis using data from several Genome-Wide Association Studies (GWAS). They used a dataset based on the study with 1.2 million study subjects for data on alcohol intake and cigarette smoking. In contrast, datasets on alcohol intake frequency and coffee consumption were obtained from the UK Biobank, encompassing hundreds of thousands of participants. The research also included large numbers of both patient and control subjects collected from the meta-analysis of OA and RA and also from the FinnGen project. The selection of instrumental variables was done carefully, focusing on single nucleotide polymorphisms (SNPs) significantly associated with each exposure.
The study assessed the genetic causality between lifestyle factors—specifically alcohol intake, smoking, and coffee consumption—and arthritis, employing MR methods and a meta-analysis of past MER studies. The meta-analysis incorporated 11 studies focusing on osteoarthritis and rheumatoid arthritis. Regarding alcohol intake, the analysis, which included results from two studies and ten MER analyses, found a non-significant positive association with arthritis overall. Subgroup analyses for OAR and RAR also showed non-significant associations. A sensitivity analysis using the weighted median method confirmed the lack of significant genetic causality between alcohol intake and arthritis. In contrast, the study found a significant positive genetic causal relationship between smoking behavior and arthritis.
The meta-analysis, using outcomes from the inverse variance weighted method, indicated a positive association between smoking and arthritis. Subgroup analyses suggested similar associations for both OAR and RAR. Sensitivity analyses using the weighted median method supported these findings. The study also revealed a positive genetic causal association between coffee consumption and arthritis. Subgroup analyses indicated stronger associations for RAR compared to OAR. Again, sensitivity analyses using the weighted median method validated these results. Overall, the study’s findings demonstrated significant positive genetic causality between both smoking and coffee consumption and arthritis (both OAR and RAR), while the evidence for a genetic causal relationship between alcohol intake and arthritis was insufficient.
These results have potential clinical implications, suggesting that individuals susceptible to osteoarthritis and patients should consider reducing smoking and coffee consumption. However, the study did not find a genetic causal relationship between alcohol intake and arthritis and, therefore, does not support the notion that alcohol might be beneficial for arthritis. The findings also offer directions for further research into the pathogenesis of arthritis.
- Edited by Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biohcemistry.
Scientific references
Wang J, Zhang B et al. Nutrients. 2023; v15(23):5009.
Chen HH, Wu PY et al. Int J Rheum Dis. 2023 Dec 7.
You JM et al. Sci Reports. 2023 Nov 26; 13(1):20768.