Polygenic analysis of the effect of common and low-frequency genetic variants on serum uric acid levels in Korean individuals
Journal
Scientific Reports
Journal Volume
10
Journal Issue
1
Date Issued
2020
Author(s)
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. ? 2020, The Author(s).
SDGs
Other Subjects
aldehyde dehydrogenase isoenzyme 2; organic anion transporter; uric acid; adult; Asian continental ancestry group; blood; chromosome 12; female; gene frequency; genetics; genome-wide association study; genotype; gout; human; hyperuricemia; male; meta analysis; middle aged; procedures; single nucleotide polymorphism; South Korea; Adult; Aldehyde Dehydrogenase, Mitochondrial; Asian Continental Ancestry Group; Chromosomes, Human, Pair 12; Female; Gene Frequency; Genome-Wide Association Study; Genotype; Gout; Humans; Hyperuricemia; Male; Middle Aged; Organic Anion Transporters; Polymorphism, Single Nucleotide; Republic of Korea; Uric Acid
Publisher
Nature Research
Type
journal article