@article{b8ddff741f9a42c9858e23d2b4b46eee,
title = "Polygenic analysis of the effect of common and low-frequency genetic variants on serum uric acid levels in Korean individuals",
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.",
author = "Cho, {Sung Kweon} and Beomsu Kim and Woojae Myung and Yoosoo Chang and Seungho Ryu and Kim, {Han Na} and Kim, {Hyung Lae} and Kuo, {Po Hsiu} and Winkler, {Cheryl A.} and Won, {Hong Hee}",
note = "Funding Information: This study was provided with biological resources from National Biobank of Korea, Centers for Disease Control and Prevention, Republic of Korea. This work was supported by the National Research Foundation of Korea (NRF) grant, funded by the Korea government (MSIT) [No. 2019R1A2C4070496], the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education [NRF-2016R1A6A3A11933380], and the Korea Health technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea [Grant Number: HI17C2372]. H.-N.K. was supported by the National Research Foundation of Korea (NRF) grant, funded by the Korea government (MSIT) [NRF-2014R1A2A2A04006291]. This research was partially supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and in part with federal funds from the National Cancer Institute, National Institutes of Health under contract [HHSN26120080001E]. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organisations in this publication imply endorsement by the U.S. Government. Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41598-020-66064-z",
language = "English",
volume = "10",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",
}