PMID- 36653889
OWN - NLM
STAT- MEDLINE
DCOM- 20230324
LR  - 20240215
IS  - 2233-6087 (Electronic)
IS  - 2233-6079 (Print)
IS  - 2233-6079 (Linking)
VI  - 47
IP  - 2
DP  - 2023 Mar
TI  - Genome-Wide Association Study on Longitudinal Change in Fasting Plasma Glucose in 
      Korean Population.
PG  - 255-266
LID - 10.4093/dmj.2021.0375 [doi]
AB  - 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 beta-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.
FAU - Jin, Heejin
AU  - Jin H
AD  - Institute of Health and Environment, Seoul National University, Seoul, Korea.
FAU - Kwak, Soo Heon
AU  - Kwak SH
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Korea.
FAU - Yoon, Ji Won
AU  - Yoon JW
AD  - Department of Internal Medicine, Seoul National University Hospital Healthcare 
      System Gangnam Center, Seoul, Korea.
FAU - Lee, Sanghun
AU  - Lee S
AD  - Department of Bioconvergence & Engineering, Dankook University, Yongin, Korea.
FAU - Park, Kyong Soo
AU  - Park KS
AD  - Department of Internal Medicine, Seoul National University Hospital, Seoul, 
      Korea.
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Korea.
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School 
      of Convergence Science and Technology, Seoul National University, Seoul, Korea.
FAU - Won, Sungho
AU  - Won S
AD  - Institute of Health and Environment, Seoul National University, Seoul, Korea.
AD  - Department of Public Health Sciences, Seoul National University, Seoul, Korea.
AD  - RexSoft Inc., Seoul, Korea.
FAU - Cho, Nam H
AU  - Cho NH
AD  - Department of Preventive Medicine, Ajou University School of Medicine, Suwon, 
      Korea.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20230119
PL  - Korea (South)
TA  - Diabetes Metab J
JT  - Diabetes & metabolism journal
JID - 101556588
RN  - 0 (Blood Glucose)
RN  - 0 (NOC3L protein, human)
SB  - IM
MH  - Humans
MH  - Blood Glucose/analysis
MH  - *Diabetes Mellitus, Type 2/epidemiology/genetics
MH  - Fasting
MH  - *Genome-Wide Association Study
MH  - Prospective Studies
MH  - Republic of Korea/epidemiology
PMC - PMC10040618
OTO - NOTNLM
OT  - Genome-wide association study
OT  - Hyperglycemia
OT  - Longitudinal studies
COIS- CONFLICTS OF INTEREST Sungho Won has no a relevant financial interest with 
      RexSoft, Inc..
EDAT- 2023/01/19 06:00
MHDA- 2023/03/24 06:00
PMCR- 2023/03/01
CRDT- 2023/01/18 23:41
PHST- 2021/12/29 00:00 [received]
PHST- 2022/04/27 00:00 [accepted]
PHST- 2023/01/19 06:00 [pubmed]
PHST- 2023/03/24 06:00 [medline]
PHST- 2023/01/18 23:41 [entrez]
PHST- 2023/03/01 00:00 [pmc-release]
AID - dmj.2021.0375 [pii]
AID - dmj-2021-0375 [pii]
AID - 10.4093/dmj.2021.0375 [doi]
PST - ppublish
SO  - Diabetes Metab J. 2023 Mar;47(2):255-266. doi: 10.4093/dmj.2021.0375. Epub 2023 
      Jan 19.