Genetic bombshell shatters gout myths: Lifestyle choices not to blame, landmark study reveals
New research challenges long-held beliefs about the causes of gout, highlighting the significant impact of genetics on the chronic inflammatory condition.
A large-scale international study has provided compelling evidence that genetics plays a more substantial role in the development of gout than previously thought, challenging the widely held belief that lifestyle choices are the primary cause. The research, led by scientists from the University of Otago, New Zealand, analysed genetic data from over 2.6 million individuals, making it one of the most comprehensive studies on gout to date.
The genome-wide association study (GWAS), published in Nature Genetics on 15 October 2024, examined amalgamated DNA datasets from various sources, with approximately 75% of the data coming from consenting customers of 23andMe, Inc., a direct-to-consumer genetics company. The researchers identified 377 genetic loci associated with gout, including 149 previously unreported loci linked to both urate levels and gout.
Professor Tony Merriman, senior author of the study from the University of Otago’s Department of Microbiology and Immunology, emphasised the importance of these findings in reshaping our understanding of gout. “Gout is a chronic disease with a genetic basis and is not the fault of the sufferer,” he stated, adding that the myth attributing gout solely to lifestyle or dietary factors needs to be dispelled.
Implications for patient care and stigma reduction
The research team hopes that these findings will help reduce the stigma associated with gout. Professor Merriman explained that the widespread misconception about gout’s causes often leads to shame among sufferers, potentially causing them to delay seeking medical attention and appropriate treatment.
While specific dietary factors can trigger gout attacks, the study underscores that the fundamental cause lies in high urate levels, crystal formation in joints, and an immune system primed to react to these crystals. The research demonstrates that genetics plays a crucial role in all of these processes.
New targets for treatment and prevention
The study’s findings have opened up new avenues for gout treatment and prevention. The researchers identified numerous immune genes and pathways that could serve as novel targets for therapeutic interventions. One potential approach highlighted in the study is the repurposing of existing drugs used for other immune-related conditions.
For instance, tocilizumab, a drug commonly used to treat rheumatoid arthritis, targets a receptor for interleukin-6, an immune signaller identified as a new gene associated with gout in this research. This discovery suggests that drugs targeting similar pathways could potentially be effective in managing gout.
Molecular mechanisms and causal factors
The GWAS provided insights into the molecular mechanisms underlying the inflammatory component of gout, which has been poorly understood until now. The researchers employed a prioritisation scheme to identify candidate genes involved in the inflammatory process of gout, including those responsible for epigenetic remodelling, cell osmolarity regulation, and modulation of NOD-like receptor protein 3 (NLRP3) inflammasome activity.
Additionally, the study utilised Mendelian randomisation analysis to provide evidence for a causal role of clonal haematopoiesis of indeterminate potential (CHIP) in gout development. This finding adds another layer of complexity to our understanding of the disease’s pathogenesis and could have implications for future treatment strategies.
Healthcare implications
Professor Merriman expressed hope that these findings will lead to improved and more accessible treatments for gout sufferers. He also emphasised the need for greater prioritisation of gout within healthcare systems, stating: “Gout deserves more health spend resource and greater prioritisation in the health system.”
The study’s results challenge the traditional view of gout as primarily a lifestyle-induced condition and highlight the importance of genetic factors in its development. This shift in understanding could lead to more targeted and effective treatments, as well as a reduction in the stigma associated with the disease.
Reference:
Merriman, T., et al. (2024). Genome-wide association study of 2.6 million people reveals genetic insights into gout pathogenesis. Nature Genetics. https://doi.org/10.1038/s41588-024-01921-5
