VIDEO: Genetic, environmental risk factors of RA

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Rheumatoid arthritis is a complex disease that has a variety of factors that lead to the risk. It starts with the genes that we inherit and we know that there is certainly a part of the risk that is hereditary. We know that because identical twins who share the exact same genes, the concordance is only around 20%, maybe as high as 40% in some studies. But obviously there's a lot that's outside of genetics in that risk. And we think that probably has to do with the environment. So we think that it starts with genetic risk. There's over 120 genes already that lead to increased risk of rheumatoid arthritis, but genetics alone is not enough. We know that being female is associated with higher risk. We believe that is because female hormones may regulate genes in such a way that leads to easier or lower threshold for the immune system to lose track and begin to attack one's own healthy joints among women. And so that's a factor that really isn't modifiable, but important for understanding risk. Over time, the environmental risk factors have modulated a bit and we're learning more and more about our gut health. And we think that dysbiosis may be one of the factors that leads to excess risk that is not well understood at this time. But we think that gut health is important. Oral health and especially periodontal disease is known to be a risk factor for rheumatoid arthritis. And that may actually be a modifiable risk factor. So trying to practice good dental hygiene, to have dental visits regularly and to seek treatment if you do have periodontal disease is very important. We've learned more recently that respiratory diseases such as having asthma or chronic obstructive pulmonary disease, and even through work of my colleagues, particularly Dr. Vanessa Krons, or working with Dr. Jeff Sparks who is at Brigham and Women's Hospital that even up upper respiratory tract disease is maybe associated with increased risk and we're planning more work to understand that relationship. So those are a few examples. We know that, of course, tobacco smoking is historically one of the major risk factors although smoking has gone down in the general population. Now, I think in terms of inhaled factors, we're turning our attention to environmental smoke or other different compounds that can be inhaled from the environment, fire, smoke, and other types of occupational exposures where there's environmental pollutants is of concern and maybe a risk factor. Different types of environmental compounds such as silica has historically been recognized as a risk factor. So as you can see, there's quite a few things that may interact with the underlying genetics to drive the risk of rheumatoid arthritis, and there are a few insights as to who we might be able to modify risk factors to diminish risk over time. Another important risk factor for rheumatoid arthritis worldwide is obesity. And overweight and obesity has been something that has grown globally over the past few decades. I'm not sure where we are and maybe it's reducing some in some recent surveys, but I think, obviously, it's still a challenge for us and it has because of its prevalence in the general population. It does play an outside risk at the population level for rheumatoid arthritis. So efforts to address obesity and overweight are welcome and may help reduce the number of cases with RA in coming decades.