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The conclusions from these essentially negative MR findings have, however, been questioned in a well-argued critique 31 , pointing out the limitations of genetic markers that explain only a small component (i.e., 7.7% at most 5 ) of serum UA variance and querying whether the core assumptions of MR, including the absence of confounds as well as a strong association with UA, are met

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A 2025 published reply from Jozwiak and colleagues argues that gain or loss of an effect under L-NAME or L-arginine is not by itself proof of nitric oxide involvement