PMID- 38356679
OWN - NLM
STAT- MEDLINE
DCOM- 20240216
LR  - 20240307
IS  - 1664-2392 (Print)
IS  - 1664-2392 (Electronic)
IS  - 1664-2392 (Linking)
VI  - 14
DP  - 2023
TI  - Observational and genetic analyses clarify the relationship between type 2 
      diabetes mellitus and gallstone disease.
PG  - 1337071
LID - 10.3389/fendo.2023.1337071 [doi]
LID - 1337071
AB  - BACKGROUND: The relationship between type 2 diabetes mellitus (T2DM) and 
      gallstone disease (GSD) have been incompletely understood. We aimed to 
      investigate their phenotypic and genetic associations and evaluate the biological 
      mechanisms underlying these associations. METHODS: We first evaluated the 
      phenotypic association between T2DM and GSD using data from the UK Biobank 
      (n>450,000) using a prospective observational design. We then conducted genetic 
      analyses using summary statistics from a meta-analysis of genome-wide association 
      studies of T2DM, with and without adjusting for body mass index (BMI) 
      (N(case)=74,124, N(control)=824,006; T2DM(adj)BMI: N(case)=50,409, 
      N(control)=523,897) and GSD (N(case)=43,639, N(control)=506,798). RESULTS: A 
      unidirectional phenotypic association was observed, where individuals with T2DM 
      exhibited a higher GSD risk (hazard ratio (HR)=1.39, P<0.001), but not in the 
      reverse direction (GSD-->T2DM: HR=1.00, P=0.912). The positive T2DM-GSD genetic 
      correlation (r(g)=0.35, P=7.71x10(-23)) remained even after adjusting for BMI 
      (T2DM(adj)BMI: r(g)=0.22, P=4.48x10(-10)). Mendelian randomization analyses 
      provided evidence of a unidirectional causal relationship (T2DM-->GSD: odds ratio 
      (OR)=1.08, P=4.6x10(-8); GSD-->T2DM: OR=1.02, P=0.48), even after adjusting for 
      important metabolic confounders (OR=1.02, P=0.02). This association was further 
      corroborated through a comprehensive functional analysis reflected by 23 
      pleiotropic single nucleotide polymorphisms, as well as multiple neural and 
      motor-enriched tissues. CONCLUSION: Through comprehensive observational and 
      genetic analyses, our study clarified the causal relationship between T2DM and 
      GSD, but not in the reverse direction. These findings might provide new insights 
      into prevention and treatment strategies for T2DM and GSD.
CI  - Copyright (c) 2024 Yan, Zhang, Yang, Zhang, Wang, Zhang, Cui, Tang, Chen, Wu, Zhao, 
      Zou, Xiao, Liu, Xiao, Yang, Zhang, Yao, Li, Liu, Yang, Jiang and Zhang.
FAU - Yan, Peijing
AU  - Yan P
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Zhang, Li
AU  - Zhang L
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Yang, Chao
AU  - Yang C
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
AD  - School of Public Health, Southwest Medical University, Luzhou, Sichuan, China.
FAU - Zhang, Wenqiang
AU  - Zhang W
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Wang, Yutong
AU  - Wang Y
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Zhang, Min
AU  - Zhang M
AD  - Clinical Research Center, Women and Children's Hospital of Chongqing Medical 
      University, Chongqing, China.
FAU - Cui, Huijie
AU  - Cui H
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Tang, Mingshuang
AU  - Tang M
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Chen, Lin
AU  - Chen L
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Wu, Xueyao
AU  - Wu X
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Zhao, Xunying
AU  - Zhao X
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Zou, Yanqiu
AU  - Zou Y
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Xiao, Jinyu
AU  - Xiao J
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Liu, Yunjie
AU  - Liu Y
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Xiao, Chenghan
AU  - Xiao C
AD  - Department of Maternal, Child and Adolescent Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
FAU - Yang, Yanfang
AU  - Yang Y
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Zhang, Ling
AU  - Zhang L
AD  - Department of Iatrical Polymer Material and Artificial Apparatus, School of 
      Polymer Science and Engineering, Sichuan University, Chengdu, China.
FAU - Yao, Yuqin
AU  - Yao Y
AD  - Department of Occupational and Environmental Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
FAU - Li, Jiayuan
AU  - Li J
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Liu, Zhenmi
AU  - Liu Z
AD  - Department of Maternal, Child and Adolescent Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
FAU - Yang, Chunxia
AU  - Yang C
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
FAU - Jiang, Xia
AU  - Jiang X
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
AD  - Department of Nutrition and Food Hygiene, West China School of Public Health and 
      West China Fourth Hospital, Sichuan University, Chengdu, China.
AD  - Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
FAU - Zhang, Ben
AU  - Zhang B
AD  - Department of Epidemiology and Biostatistics, Institute of Systems Epidemiology, 
      and West China-PUMC C. C. Chen Institute of Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, Sichuan, 
      China.
AD  - Department of Occupational and Environmental Health, West China School of Public 
      Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Research Support, Non-U.S. Gov't
DEP - 20240131
PL  - Switzerland
TA  - Front Endocrinol (Lausanne)
JT  - Frontiers in endocrinology
JID - 101555782
SB  - IM
MH  - Humans
MH  - Body Mass Index
MH  - *Diabetes Mellitus, Type 2/epidemiology/genetics/complications
MH  - *Gallstones/epidemiology/genetics
MH  - Genome-Wide Association Study
MH  - Mendelian Randomization Analysis
PMC - PMC10864641
OTO - NOTNLM
OT  - Mendelian randomization
OT  - bidirectional
OT  - causal relationship
OT  - cohort
OT  - gallstone disease
OT  - genetic association
OT  - type 2 diabetes mellitus
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/02/15 06:42
MHDA- 2024/02/16 06:42
PMCR- 2023/01/01
CRDT- 2024/02/15 04:01
PHST- 2023/11/12 00:00 [received]
PHST- 2023/12/26 00:00 [accepted]
PHST- 2024/02/16 06:42 [medline]
PHST- 2024/02/15 06:42 [pubmed]
PHST- 2024/02/15 04:01 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fendo.2023.1337071 [doi]
PST - epublish
SO  - Front Endocrinol (Lausanne). 2024 Jan 31;14:1337071. doi: 
      10.3389/fendo.2023.1337071. eCollection 2023.