Smoking Status and Type 2 Diabetes, and Cardiovascular Disease: A Comprehensive Analysis of Shared Genetic Etiology and Causal Relationship.
Smoking Status and Type 2 Diabetes, and Cardiovascular Disease: A Comprehensive Analysis of Shared Genetic Etiology and Causal Relationship.
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DOI：
10.3389/fendo.2022.809445
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发表时间：
2022
影响因子：
5.2
通讯作者：
Huang T
中科院分区：
文献类型：
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作者：
Chi Y;Wang X;Jia J;Huang T
本研究旨在探讨吸烟状况与2型糖尿病(T2D)、心血管疾病(CVDS)及相关代谢特征之间的共同遗传病因及其因果关系。使用公开的全基因组关联研究(GWAS)的汇总统计数据，我们用连锁不平衡分数回归(LDSC)分析估计了吸烟状况与T2D、6种主要心血管疾病和8个相关代谢性状的遗传相关性；用大规模全基因组跨性状荟萃分析确定了共同的遗传基因座；通过一系列GWAS后分析探索了潜在的共同生物学机制；并用孟德尔随机化(MR)确定了因果关系。我们发现吸烟与T2D(Rg=0.170，p=9.39×10−22)、冠状动脉疾病(Rg=0.234，p=1.96×10−27)、心肌梗死(MI)(Rg=0.226，p=1.08×10−17)和心力衰竭(HF)(Rg=0.276，p=8.43×10−20)呈显著正相关。对吸烟状态的跨性状Meta分析和转录组关联分析发现，与T2D相关的基因座有210个(32个新基因座)和354个基因组织对，与冠心病相关的63个座位(12个新基因座)和37个基因组织对，与MI相关的38个座位(6个新基因座)和17个基因组织对，与HF相关的28个基因座(3个新基因座)和1个基因组织对。这些共有的基因座在外/内分泌、心血管、神经、消化和生殖系统中都很丰富。此外，我们还观察到吸烟状况与T2D(β=0.385，p=3.31×10−3)、冠心病(β=0.670，p=7.86×10−11)、MI(β=0.725，p=2.32×10−9)和心衰(β=0.520，p=1.53×10−6)的高风险相关。我们的发现为吸烟状态与T2D、CAD、MI和HF之间的共同遗传病因和因果关系提供了强有力的证据，强调了吸烟与T2D和心血管疾病之间潜在的共同生物学机制。这项工作为更有效、更及时地预防吸烟相关的T2D和心血管疾病开辟了一条新的途径。
This study aimed to explore shared genetic etiology and the causality between smoking status and type 2 diabetes (T2D), cardiovascular diseases (CVDs), and related metabolic traits. Using summary statistics from publicly available genome-wide association studies (GWASs), we estimated genetic correlations between smoking status and T2D, 6 major CVDs, and 8 related metabolic traits with linkage disequilibrium score regression (LDSC) analysis; identified shared genetic loci with large-scale genome-wide cross-trait meta-analysis; explored potential shared biological mechanisms with a series of post-GWAS analyses; and determined causality with Mendelian randomization (MR). We found significant positive genetic associations with smoking status for T2D (Rg = 0.170, p = 9.39 × 10−22), coronary artery disease (CAD) (Rg = 0.234, p = 1.96 × 10−27), myocardial infarction (MI) (Rg = 0.226, p = 1.08 × 10−17), and heart failure (HF) (Rg = 0.276, p = 8.43 × 10−20). Cross-trait meta-analysis and transcriptome-wide association analysis of smoking status identified 210 loci (32 novel loci) and 354 gene–tissue pairs jointly associated with T2D, 63 loci (12 novel loci) and 37 gene–tissue pairs with CAD, 38 loci (6 novel loci) and 17 gene–tissue pairs with MI, and 28 loci (3 novel loci) and one gene–tissue pair with HF. The shared loci were enriched in the exo-/endocrine, cardiovascular, nervous, digestive, and genital systems. Furthermore, we observed that smoking status was causally related to a higher risk of T2D (β = 0.385, p = 3.31 × 10−3), CAD (β = 0.670, p = 7.86 × 10−11), MI (β = 0.725, p = 2.32 × 10−9), and HF (β = 0.520, p = 1.53 × 10−6). Our findings provide strong evidence on shared genetic etiology and causal associations between smoking status and T2D, CAD, MI, and HF, underscoring the potential shared biological mechanisms underlying the link between smoking and T2D and CVDs. This work opens up a new way of more effective and timely prevention of smoking-related T2D and CVDs.
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影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
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作者：
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通讯作者：
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影响因子：
8.2
作者：
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通讯作者：
Groop, L.
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影响因子：
7.7
作者：
Bergman BC;Perreault L;Hunerdosse D;Kerege A;Playdon M;Samek AM;Eckel RH
通讯作者：
Eckel RH
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
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