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肥胖和血脂异常与 2 型糖尿病的因果关系:两样本 Mendelian 随机研究。

Causal Association of Obesity and Dyslipidemia with Type 2 Diabetes: A Two-Sample Mendelian Randomization Study.

机构信息

Veterans Medical Research Institute, Veterans Health Service Medical Center, Seoul 05368, Republic of Korea.

Department of Applied Statistics, Chung-Ang University, Seoul 06974, Republic of Korea.

出版信息

Genes (Basel). 2022 Dec 19;13(12):2407. doi: 10.3390/genes13122407.


DOI:10.3390/genes13122407
PMID:36553674
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9777695/
Abstract

Recent studies have suggested an association between obesity and dyslipidemia in the development of type 2 diabetes (T2D). The purpose of this study was to explore the causal effects of obesity and dyslipidemia on T2D risk in Asians. Two-sample Mendelian randomization (MR) analyses were performed to assess genetically predicted obesity using body mass index (BMI) and dyslipidemia using high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TCHL), and triglycerides (TG) versus T2D susceptibility using genome-wide association study (GWAS) results derived from the summary statistics of Biobank Japan ( = 179,000) and DIAbetes Meta-ANalysis of Trans-Ethnic association studies ( = 50,533). The MR analysis demonstrated evidence of a causal effect of higher BMI on the risk of T2D (odds ratio (OR) > 1.0, < 0.05). In addition, TG showed a protective effect on the risk of T2D (ORs 0.68-0.85). However, HDL, LDL, and TCHL showed little genetic evidence supporting a causal association between dyslipidemia and T2D. We found strong genetic evidence supporting a causal association of BMI with T2D. Although HDL, LDL, and TCHL did not show a causal association with T2D, TG had a causal relationship with the decrease of T2D. Although it was predicted that TG would be linked to a higher risk of T2D, it actually exhibited a paradoxical protective effect against T2D, which requires further investigation.

摘要

最近的研究表明,肥胖和血脂异常与 2 型糖尿病(T2D)的发生有关。本研究旨在探讨肥胖和血脂异常对亚洲人 T2D 风险的因果影响。采用两样本 Mendelian 随机化(MR)分析,使用体重指数(BMI)预测肥胖,使用高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)、总胆固醇(TCHL)和甘油三酯(TG)预测血脂异常,使用全基因组关联研究(GWAS)结果评估肥胖和血脂异常与 T2D 易感性的关系。来自日本生物银行(=179000)和跨种族糖尿病荟萃分析研究(=50533)的汇总统计数据。MR 分析表明,较高的 BMI 与 T2D 风险呈正相关(优势比(OR)>1.0, <0.05)。此外,TG 对 T2D 风险具有保护作用(ORs 0.68-0.85)。然而,HDL、LDL 和 TCHL 对血脂异常与 T2D 之间存在因果关系的遗传证据很少。我们发现了强有力的遗传证据支持 BMI 与 T2D 之间存在因果关系。尽管 HDL、LDL 和 TCHL 与 T2D 之间没有因果关系,但 TG 与 T2D 的降低有因果关系。尽管预测 TG 与 T2D 的风险增加有关,但实际上它对 T2D 具有保护作用,这需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/9777695/b35ba636fb44/genes-13-02407-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/9777695/750c12cfdd48/genes-13-02407-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/9777695/40ffcb50ea90/genes-13-02407-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/9777695/40cd32309ea8/genes-13-02407-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/9777695/b35ba636fb44/genes-13-02407-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/9777695/750c12cfdd48/genes-13-02407-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/9777695/40ffcb50ea90/genes-13-02407-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/9777695/40cd32309ea8/genes-13-02407-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ae/9777695/b35ba636fb44/genes-13-02407-g004.jpg

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本文引用的文献

[1]
Identification of genetic effects underlying type 2 diabetes in South Asian and European populations.

Commun Biol. 2022-4-7

[2]
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Nat Genet. 2021-10

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Diabetologia. 2020-11

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Wellcome Open Res. 2023-8-4

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Association between interarm blood pressure differences and diabetic retinopathy in patients with type 2 diabetes.

Diab Vasc Dis Res. 2020

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Causal Effects of Overall and Abdominal Obesity on Insulin Resistance and the Risk of Type 2 Diabetes Mellitus: A Two-Sample Mendelian Randomization Study.

Front Genet. 2020-7-2

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[9]
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Res Synth Methods. 2019-4-23

[10]
Publisher Correction: Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.

Nat Genet. 2018-8

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