Single-nucleotide polymorphisms link gout with health-related lifestyle factors in Korean cohorts

PLoS One. 2023 Dec 7;18(12):e0295038. doi: 10.1371/journal.pone.0295038. eCollection 2023.

Abstract

Gout-a very painful inflammatory arthritis caused by the deposition of monosodium urate crystals in the joints-is influenced by several factors. We identified the association of single- nucleotide polymorphisms (SNPs) that link gout with health-related lifestyle factors using genomic data from the Korean Genome and Epidemiology Study. We conducted a genome-wide association study (GWAS) on 18,927 samples of 438 Korean patients with gout and 18,489 controls for the discovery stage. For the replication stage, another batch containing samples of 326 patients with gout and 2,737 controls were analyzed. Lastly, a meta-analysis was performed using these two cohorts. We analyzed the effects of health-related lifestyle factors, including eating habits, physical activity, drinking behavior, and smoking behavior, on gout. After identifying the association between GWAS-derived SNPs and health-related lifestyle factors, we confirmed the interaction between the polygenic risk score (PRS) and health-related lifestyle factors. We identified 15 SNPs related to gout, among which rs1481012 of ABCG2 located on chromosome 4 has been newly discovered (P = 2.46e-11). On examining the interaction between SNPs and health-related lifestyles, rs3109823-located in ABCG2-was found to be associated with smoking status. In addition, rs11936395-located in SLC2A9-was significantly associated with the average momentum of exercise per session, whereas rs11066325 located in PTPN11, showed a significant association with the number of exercise sessions per week, smoking status, drinking status, and amount of soju drink per session. rs9421589-located in FAM35A-was significantly associated with the duration of smoking. In addition, we verified that the association between PRS and duration of smoking affects gout. Thus, in this study, we identified novel SNPs that link gout with health-related lifestyle factors in the Korean population.

Publication types

  • Meta-Analysis

MeSH terms

  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Glucose Transport Proteins, Facilitative / genetics
  • Gout* / epidemiology
  • Gout* / genetics
  • Humans
  • Life Style
  • Polymorphism, Single Nucleotide*
  • Republic of Korea / epidemiology
  • Risk Factors
  • Uric Acid

Substances

  • Uric Acid
  • SLC2A9 protein, human
  • Glucose Transport Proteins, Facilitative

Grants and funding

This study was supported by a National Research Foundation of Korea grant funded by Korea government (MSIT) (grant no. NRF-2019R1F1A1062965 and no. NRF-2022R1F1A1068307). The funder did not participate in the study's design, data collection and analysis, publication decision, or manuscript preparation. There was no additional external funding received for this study.