Polygenic analysis of the effect of common and low-frequency genetic variants on serum uric acid levels in Korean individuals.

Scientific Reports
Sung Kweon ChoHong-Hee Won

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 ethnica...Continue Reading

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Citations

May 1, 2021·Current Opinion in Clinical Nutrition and Metabolic Care·Kendra L Nelson, Venkata Saroja Voruganti
Jul 23, 2021·Electrolyte & Blood Pressure : E & BP·Sungjin Chung, Gheun-Ho Kim

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Methods Mentioned

BETA
chip

Software Mentioned

Eagle
KING
Minimac3
COJO
PLINK
METAL
ANNOVAR
GCTA

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