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

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. Choi, Tony R. Merriman, Young Jin Kim () and Hong-Hee Won ()
Additional contact information
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
Hyon K. Choi: Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School
Tony R. Merriman: University of Otago
Young Jin Kim: National Institute of Health
Hong-Hee Won: Sungkyunkwan University, Samsung Medical Center

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47805-4

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