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Heejin Jin 1 Article
Genetics
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Genome-Wide Association Study on Longitudinal Change in Fasting Plasma Glucose in Korean Population
Heejin Jin, Soo Heon Kwak, Ji Won Yoon, Sanghun Lee, Kyong Soo Park, Sungho Won, Nam H. Cho
Diabetes Metab J. 2023;47(2):255-266.   Published online January 19, 2023
DOI: https://doi.org/10.4093/dmj.2021.0375
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Background
Genome-wide association studies (GWAS) on type 2 diabetes mellitus (T2DM) have identified more than 400 distinct genetic loci associated with diabetes and nearly 120 loci for fasting plasma glucose (FPG) and fasting insulin level to date. However, genetic risk factors for the longitudinal deterioration of FPG have not been thoroughly evaluated. We aimed to identify genetic variants associated with longitudinal change of FPG over time.
Methods
We used two prospective cohorts in Korean population, which included a total of 10,528 individuals without T2DM. GWAS of repeated measure of FPG using linear mixed model was performed to investigate the interaction of genetic variants and time, and meta-analysis was conducted. Genome-wide complex trait analysis was used for heritability calculation. In addition, expression quantitative trait loci (eQTL) analysis was performed using the Genotype-Tissue Expression project.
Results
A small portion (4%) of the genome-wide single nucleotide polymorphism (SNP) interaction with time explained the total phenotypic variance of longitudinal change in FPG. A total of four known genetic variants of FPG were associated with repeated measure of FPG levels. One SNP (rs11187850) showed a genome-wide significant association for genetic interaction with time. The variant is an eQTL for NOC3 like DNA replication regulator (NOC3L) gene in pancreas and adipose tissue. Furthermore, NOC3L is also differentially expressed in pancreatic β-cells between subjects with or without T2DM. However, this variant was not associated with increased risk of T2DM nor elevated FPG level.
Conclusion
We identified rs11187850, which is an eQTL of NOC3L, to be associated with longitudinal change of FPG in Korean population.

Citations

Citations to this article as recorded by  
  • Unraveling the understudied influence of a lead variant in the 9p21 locus on the atherogenic index among type 2 diabetes patients with coronary artery disease
    Mahsa Naserian, Ahad Alizadeh, Mani Nosrati, Abdolkarim Mahrooz
    Journal of Diabetes & Metabolic Disorders.2024;[Epub]     CrossRef
  • Abdominal aortic aneurysm and cardiometabolic traits share strong genetic susceptibility to lipid metabolism and inflammation
    Shufen Zheng, Philip S. Tsao, Cuiping Pan
    Nature Communications.2024;[Epub]     CrossRef

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