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Large-scale cross-ancestry genome-wide meta-analysis of serum urate

Author

Listed:
  • Chamlee Cho

    (Sungkyunkwan University, Samsung Medical Center)

  • Beomsu Kim

    (Sungkyunkwan University, Samsung Medical Center)

  • Dan Say Kim

    (Sungkyunkwan University, Samsung Medical Center)

  • Mi Yeong Hwang

    (National Institute of Health)

  • Injeong Shim

    (Sungkyunkwan University, Samsung Medical Center)

  • Minku Song

    (Sungkyunkwan University, Samsung Medical Center)

  • Yeong Chan Lee

    (Samsung Medical Center)

  • Sang-Hyuk Jung

    (University of Pennsylvania)

  • Sung Kweon Cho

    (Ajou University School of Medicine (AUSOM))

  • Woong-Yang Park

    (Samsung Medical Center, Sungkyunkwan University School of Medicine)

  • Woojae Myung

    (Seoul National University Bundang Hospital)

  • Bong-Jo Kim

    (National Institute of Health)

  • Ron Do

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Hyon K. Choi

    (Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School)

  • Tony R. Merriman

    (University of Otago
    University of Alabama at Birmingham)

  • Young Jin Kim

    (National Institute of Health)

  • Hong-Hee Won

    (Sungkyunkwan University, Samsung Medical Center
    Samsung Medical Center, Sungkyunkwan University School of Medicine)

Abstract

Hyperuricemia is an essential causal risk factor for gout and is associated with cardiometabolic diseases. Given the limited contribution of East Asian ancestry to genome-wide association studies of serum urate, the genetic architecture of serum urate requires exploration. A large-scale cross-ancestry genome-wide association meta-analysis of 1,029,323 individuals and ancestry-specific meta-analysis identifies a total of 351 loci, including 17 previously unreported loci. The genetic architecture of serum urate control is similar between European and East Asian populations. A transcriptome-wide association study, enrichment analysis, and colocalization analysis in relevant tissues identify candidate serum urate-associated genes, including CTBP1, SKIV2L, and WWP2. A phenome-wide association study using polygenic risk scores identifies serum urate-correlated diseases including heart failure and hypertension. Mendelian randomization and mediation analyses show that serum urate-associated genes might have a causal relationship with serum urate-correlated diseases via mediation effects. This study elucidates our understanding of the genetic architecture of serum urate control.

Suggested Citation

  • Chamlee Cho & Beomsu Kim & Dan Say Kim & Mi Yeong Hwang & Injeong Shim & Minku Song & Yeong Chan Lee & Sang-Hyuk Jung & Sung Kweon Cho & Woong-Yang Park & Woojae Myung & Bong-Jo Kim & Ron Do & Hyon K., 2024. "Large-scale cross-ancestry genome-wide meta-analysis of serum urate," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47805-4
    DOI: 10.1038/s41467-024-47805-4
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