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, Hong Hee Won

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Article number3441
JournalNature Communications
Volume15
Issue number1
DOIs
StatePublished - Dec 2024

Fingerprint

Dive into the research topics of 'Large-scale cross-ancestry genome-wide meta-analysis of serum urate'. Together they form a unique fingerprint.

Cite this