The Causal Relationship of Multiple Sclerosis on Serum Uric Acid Levels: A Mendelian Randomization Study

Abstract

Multiple sclerosis (MS) poses a significant challenge in global health, with increasing incidence rates and profound implications that transcend the geographical boundaries. Recent literature has explored the relationship between MS and serum uric acid (SUA) levels, yielding inconclusive findings. A high SUA level is associated with several chronic disorders and has planetary health significance. Explaining person-to-person variations in SUA is therefore important. In this overarching context, despite a multitude of studies on the putative MS and SUA relationship, limitations such as small sample sizes and inconsistent outcomes persist, highlighting the current gaps in understanding this complex relationship. Here, we report a two-sample Mendelian randomization (MR) study that was conducted to estimate causal effects between MS as the exposure and SUA as the outcome. Our analysis leveraged extensive cohort datasets from publicly accessible genome-wide association studies. The inverse variance weighted method in MR indicated that the odds ratios (ORs) of SUA level per unit increase for MS were 1.649 (95% confidence interval [CI] of OR: 1.09–2.488; p = 0.017) and 23.11 (95% CI of OR: 7.04–75.84; p = 2.23 × 10⁻⁷). Leave-one-out sensitivity analyses, horizontal pleiotropy, and Cochran’s Q tests showed robustness of results. This study offers support for a causal association between MS incidence and elevated SUA levels. Pleiotropic tests and sensitivity analyses confirmed minimal horizontal pleiotropy effects and the robustness of the causal association. This MR study provides a causal effect between the incidence of MS and SUA level increase.