Genome-wide Association Study of Liver-related Enzymes Suggests Putative Pleiotropic Effects on Diverse Traits and Diseases.
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ABSTRACT:
SUBMITTER: Kim HS
PROVIDER: S-EPMC8744143 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
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Genome-wide Association Study of Liver-related Enzymes Suggests Putative Pleiotropic Effects on Diverse Traits and Diseases.
Kim Hyun-Seok HS Sookoian Silvia S Hernaez Ruben R
Hepatology (Baltimore, Md.) 20211201 6
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Project description:Liver enzyme elevations, as an indicator of liver function, are widely associated with metabolic diseases. Genome-wide population-based association studies have identified a genetic susceptibility to liver enzyme elevations and their related traits; however, the genetic architecture in childhood remains largely unknown. We performed a genome-wide association study to identify new genetic loci for liver enzyme levels in a Korean childhood cohort (n = 484). We observed three novel loci (rs4949718, rs80311637, and rs596406) that were multiply associated with elevated levels of alanine transaminase and aspartate transaminase. Although there are some limitations, including genetic power, additional replication and functional characterization will support the clarity on the genetic contribution that the ST6GALNAC3, ADAMTS9, and CELF2 genes have in childhood liver function.
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Project description:BackgroundAlthough genetic features vary across ethnicities, few genome-wide association studies (GWAS) have reported the genetic determinants of liver enzyme expression. This study was aimed to evaluate the associations of genome-wide single nuclear polymorphisms (SNPs) with the liver enzymes in a Korean population.MethodsWe performed a GWAS to identify genetic loci influencing liver function, as measured by concentrations of alkaline phosphatase (ALP), alanine transaminase (ALT), gamma-glutamyl transferase (GGT) and total bilirubin (BIL) in in Korean study participants.ResultsA total of 6,488 subjects (4,457 in the discovery and 2,031 in the validation set) were included. The mean subject age was 50.0±10.6 years (male, 53.7%). Among a total of 546,738 SNPs tested, rs651007 and rs579459 located in the ABO gene showed strong associations with ALP (P = 1.63×10-8 and 5.61×10-8, respectively [discovery set]; P = 4.08×10-15 and 9.92×10-16, respectively [validation set]). Additionally, rs5751901 and rs2006092, which are located in the GGT1 gene, showed strong associations with GGT (P = 6.44×10-15 and 1.26×10-15, respectively [discovery set]; P = 4.13×10-10 and 5.15×10-11, respectively [validation set]). Among the 13 SNPs that showed genome-wide significance with total bilirubin levels, rs10929302 and rs6742078 showed the most significant association (P = 3.08×10-64 and 2.05×10-62, respectively [discovery set]; P = 1.33×10-116 and 2.24×10-118, respectively [validation set]). No genome-wide significant associations was found for ALT.ConclusionsWe demonstrated that ABO, GGT1 and UGT1A family were associated with ALP, GGT and BIL, respectively in Korean population. These findings differ from reported results in GWAS in European populations in terms of associated genes and locations, suggesting different genetic mechanisms of liver enzyme regulation according to ethnicity.
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