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Genetically predicted serum urate levels have no causal role on depression or other psychiatric disorders

Sizheng Steven Zhao1, Yu Qian2, Sarah L Mackie3,4

  • 1Musculoskeletal Biology, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.

Clinical Rheumatology
|March 31, 2021
PubMed

Insights

This study found no causal link between genetically predicted serum urate levels and major depressive disorder or anxiety. These findings suggest current gout management guidelines may need reevaluation regarding serum urate targets.

Area of Science:

  • Genetics and Psychiatry
  • Metabolic Disorders
  • Epidemiology

Background:

  • Observational studies suggest a link between low serum urate and neuropsychiatric diseases, prompting caution in gout management.
  • The potential causal relationship between serum urate levels and psychiatric disorders remains unclear.

Purpose of the Study:

  • To investigate the causal effect of genetically predicted serum urate levels on the risk of major depressive disorder (MDD) and anxiety.
  • To explore the association between serum urate and other psychiatric conditions including bipolar disorder, PTSD, OCD, ADHD, schizophrenia, and anorexia nervosa.

Main Methods:

  • Utilized two-sample Mendelian randomization (MR) with genome-wide association study (GWAS) data.
  • Identified 30 single-nucleotide polymorphisms (SNPs) associated with serum urate in 110,347 individuals.
  • Applied random-effects inverse variance-weighted method and sensitivity analyses for robustness.

Main Results:

  • Genetically predicted serum urate levels showed no causal association with the risk of major depressive disorder (MDD) (OR 0.98; 95% CI 0.94, 1.03).
  • No causal link was observed for anxiety (OR 0.90; 95% CI 0.80, 1.02) or other psychiatric disorders (OR range 0.95 to 1.06).
  • Sensitivity analyses confirmed the absence of a causal relationship.

Conclusions:

  • This study provides no evidence for a causal effect of genetically predicted serum urate on the risk of MDD, anxiety, or other psychiatric disorders.
  • Findings challenge the caution advised for reducing serum urate levels in gout management based on observational data.
  • Clinical guidelines on serum urate targets for gout may require reconsideration in light of these genetic findings.
Keywords:
AnxietyDepressionGoutMendelian randomizationMental healthUrate

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