Whenever I am asked what I do for a living there is a moment before I respond where I wonder how much detail I should give. This is because, inevitably, if I mention that I research the genetics of gout, the response is: “Gout, my [relative / friend] has that. Is it genetic? I thought you got it from drinking too much beer.” This perception of gout as a self-inflicted disease is prominent amongst the general community. In my conversations with gout patients, diet is particularly mentioned as a trigger of gout flares or as a disease management tool. It is not surprising that diet is so commonly linked to gout. Indeed, from the 16th to early 18th century having gout was considered a marker of wealth and status, as only the wealthy had the means to overindulge in enough alcohol or rich foods to suffer a gout flare. The prevalence of gout among members of the royal families of Europe during this time further solidified this belief. The genetic aspect of gout is, of course, evident in this history of the royal family, but the attribution of this disease to eating rich foods is so prominent that gout and diet have become almost completely inter-linked.
With our modern understanding of the genetics of gout, there was a real need for a study that considered the roles of both diet and genetics. Many studies have looked at specific food items and their relationship with gout or raised serum urate (a necessary precursor to the development of gout), particularly those foods that have been anecdotally linked to gout flares for the past 2,000 years. Our study, published in The BMJ, takes these analyses one step further. It focuses on the relationship between diet and serum urate, and along with assessing the correlation between serum urate and all of the food items available in our cohort (in what we have called a “Diet-Wide Association Study” or “DWAS”) our study also assesses how much variation in serum urate each food item explains.
This analysis, unsurprisingly, identified correlations between serum urate levels and many foods that had shown significant associations before (along with identifying several novel associations requiring follow-up). However, much more notably our study found that none of these food items explained more than 1% of the variation in serum urate levels amongst the study population. And when the analysis was extended to consider several estimates of overall dietary habits these also explained very little variation in serum urate levels, less than half a percent (0.15% to 0.28%). In contrast, genetic variants explained substantially more of the variation in serum urate within our study population. The most strongly associated single genetic variant (from the SLC2A9 gene) explained ~4% of the variation in serum urate. Even more strikingly, when the whole genome was considered, over 20% of the variation in serum urate was explained.
It came as no surprise to us that genetic factors have a larger influence on serum urate than dietary factors, what did surprise us was the magnitude of this difference, an almost 100-fold increase. Overall diet explaining less than 0.5% of the variation in serum urate is a profoundly small influence considering that diet is so intrinsically associated with gout. As this study was conducted in a “healthy population” replication in a cohort of gout patients is necessary; however, for diet to explain so little of such an essential component in gout aetiology is an important finding. And if the follow-on analyses in gout patients find a similar difference in the magnitude of effect between genetics and diet this work will have provided me with an answer to those people asking “Gout, is that genetic?” A very definite yes. Gout is genetic, and “drinking too much beer” has very little influence on serum urate.
Tanya Major (@geeketics) is a Post-Doctoral Fellow at the University of Otago in Dunedin, New Zealand. Her research focuses on the genetic, dietary, and environmental factors involved in the onset and progression of gout. She aims to use her research to improve gout treatment and quality of life for gout patients.
Competing interests: See full disclosure on the research paper.