Abstract

Increased serum uric acid (SUA) levels cause gout and are associated with multiple diseases, including chronic kidney disease. Previous genome-wide association studies (GWAS) have identified more than 180 loci that contribute to SUA levels. Here, we investigated genetic determinants of SUA level in the Korean population. We conducted a GWAS for SUA in 6,881 Korean individuals, calculated polygenic risk scores (PRSs) for common variants, and validated the association of low-frequency variants and PRS with SUA levels in 3,194 individuals. We identified two low-frequency and six common independent variants associated with SUA. Despite the overall similar effect sizes of variants in Korean and European populations, the proportion of variance for SUA levels explained by the variants was greater in the Korean population. A rare, nonsense variant SLC22A12 p.W258X showed the most significant association with reduced SUA levels, and PRSs of common variants associated with SUA levels were significant in multiple Korean cohorts. Interestingly, an East Asian-specific missense variant (rs671) in ALDH2 displayed a significant association on chromosome 12 with the SUA level. Further genetic epidemiological studies on SUA are needed in ethnically diverse cohorts to investigate rare or low-frequency variants and determine the influence of genetic and environmental factors on SUA.

Details

Title
Polygenic analysis of the effect of common and low-frequency genetic variants on serum uric acid levels in Korean individuals
Author
Cho, Sung Kweon 1   VIAFID ORCID Logo  ; Kim Beomsu 2   VIAFID ORCID Logo  ; Woojae, Myung 3 ; Chang Yoosoo 4   VIAFID ORCID Logo  ; Ryu Seungho 4   VIAFID ORCID Logo  ; Han-Na, Kim 5 ; Kim, Hyung-Lae 6 ; Kuo Po-Hsiu 7 ; Winkler, Cheryl A 8 ; Hong-Hee, Won 2   VIAFID ORCID Logo 

1  Sungkyunkwan University, Samsung Medical Center, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Seoul, Republic of Korea; Molecular Genetic Epidemiology Section, Basic Research Program, Frederick National Laboratory for Cancer Research, Frederick, USA (GRID:grid.418021.e) (ISNI:0000 0004 0535 8394) 
2  Sungkyunkwan University, Samsung Medical Center, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Seoul, Republic of Korea (GRID:grid.418021.e) 
3  Seoul National University Bundang Hospital, Department of Neuropsychiatry, Seongnam-si, Republic of Korea (GRID:grid.412480.b) (ISNI:0000 0004 0647 3378) 
4  Sungkyunkwan University School of Medicine, Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Seoul, Republic of Korea (GRID:grid.264381.a) (ISNI:0000 0001 2181 989X) 
5  Sungkyunkwan University School of Medicine, Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Seoul, Republic of Korea (GRID:grid.264381.a) (ISNI:0000 0001 2181 989X); Sungkyunkwan University School of Medicine, Medical Research Institute, Kangbuk Samsung Hospital, Seoul, Republic of Korea (GRID:grid.264381.a) (ISNI:0000 0001 2181 989X) 
6  Ewha Womans University, Department of Biochemistry, Seoul, Republic of Korea (GRID:grid.255649.9) (ISNI:0000 0001 2171 7754) 
7  National Taiwan University, Department of Public Health & Institute of Epidemiology and Preventive Medicine, College of Public Health, Taipei, Taiwan (GRID:grid.19188.39) (ISNI:0000 0004 0546 0241) 
8  Molecular Genetic Epidemiology Section, Basic Research Program, Frederick National Laboratory for Cancer Research, Frederick, USA (GRID:grid.418021.e) (ISNI:0000 0004 0535 8394) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-020-66064-z
ProQuest document ID
2410659343
Copyright
© The Author(s) 2020. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.