Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.
Type 2 Diabetes, Metabolic Traits, and Risk of Heart Failure: A Mendelian Randomization Study.
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DOI：
10.2337/dc20-2518
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发表时间：
2021-07
期刊：
影响因子：
16.2
通讯作者：
HERMES Consortium
中科院分区：
文献类型：
--
作者：
Mordi IR;Lumbers RT;Palmer CNA;Pearson ER;Sattar N;Holmes MV;Lang CC;HERMES Consortium
本研究的目的是利用孟德尔随机化 (MR) 技术来估计 2 型糖尿病 (T2D) 的遗传易感性、血糖特征和心力衰竭 (HF) 风险之间的因果关系。摘要水平数据来自 T2D、胰岛素抵抗 (IR)、糖化血红蛋白、空腹胰岛素和血糖以及心力衰竭的全基因组关联研究。 MR 采用逆方差加权法进行。敏感性分析包括 MR-Egger 方法、加权中值和众数方法以及对潜在介质的多变量 MR 调节。 T2D 的遗传易感性与较高的 HF 风险存在因果关系（每 1 个对数单位较高的 T2D 风险，比值比 [OR] 1.13；95% CI 1.11–1.14；P < 0.001）；然而，敏感性分析揭示了定向多效性的证据。在多变量 MR 中调整冠心病、BMI、LDL 胆固醇和血压后，T2D 和 HF 之间的关系减弱。基因检测较高的 IR 与较高的 HF 风险相关（每 1 个对数单位的 IR 风险越高，OR 为 1.19；95% CI 1.00–1.41；P = 0.041）。空腹胰岛素、血糖或糖化血红蛋白与心力衰竭风险之间没有发现显着关联。心力衰竭的遗传易感性与较高的 T2D 风险存在因果关系（OR 1.49；95% CI 1.01-2.19；P = 0.042），尽管同样有多效性的证据。这些发现表明 T2D 和 IR 在 HF 病因学中可能具有因果作用，尽管双向效应和定向多效性的存在凸显了必须考虑的潜在偏差来源。
The aim of this study was to use Mendelian randomization (MR) techniques to estimate the causal relationships between genetic liability to type 2 diabetes (T2D), glycemic traits, and risk of heart failure (HF). Summary-level data were obtained from genome-wide association studies of T2D, insulin resistance (IR), glycated hemoglobin, fasting insulin and glucose, and HF. MR was conducted using the inverse-variance weighted method. Sensitivity analyses included the MR-Egger method, weighted median and mode methods, and multivariable MR conditioning on potential mediators. Genetic liability to T2D was causally related to higher risk of HF (odds ratio [OR] 1.13 per 1-log unit higher risk of T2D; 95% CI 1.11–1.14; P < 0.001); however, sensitivity analysis revealed evidence of directional pleiotropy. The relationship between T2D and HF was attenuated when adjusted for coronary disease, BMI, LDL cholesterol, and blood pressure in multivariable MR. Genetically instrumented higher IR was associated with higher risk of HF (OR 1.19 per 1-log unit higher risk of IR; 95% CI 1.00–1.41; P = 0.041). There were no notable associations identified between fasting insulin, glucose, or glycated hemoglobin and risk of HF. Genetic liability to HF was causally linked to higher risk of T2D (OR 1.49; 95% CI 1.01–2.19; P = 0.042), although again with evidence of pleiotropy. These findings suggest a possible causal role of T2D and IR in HF etiology, although the presence of both bidirectional effects and directional pleiotropy highlights potential sources of bias that must be considered.
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DOI：
10.1161/circheartfailure.115.002560
发表时间：
2016-01
期刊：
Circulation. Heart failure
影响因子：
--
作者：
Kristensen SL;Preiss D;Jhund PS;Squire I;Cardoso JS;Merkely B;Martinez F;Starling RC;Desai AS;Lefkowitz MP;Rizkala AR;Rouleau JL;Shi VC;Solomon SD;Swedberg K;Zile MR;McMurray JJ;Packer M;PARADIGM-HF Investigators and Committees
通讯作者：
PARADIGM-HF Investigators and Committees
综合基因组分析暗示有限的外周脂肪储存能力在人类胰岛素抵抗的发病机理中。
影响因子：
30.8
作者：
Lotta LA;Gulati P;Day FR;Payne F;Ongen H;van de Bunt M;Gaulton KJ;Eicher JD;Sharp SJ;Luan J;De Lucia Rolfe E;Stewart ID;Wheeler E;Willems SM;Adams C;Yaghootkar H;EPIC-InterAct Consortium;Cambridge FPLD1 Consortium;Forouhi NG;Khaw KT;Johnson AD;Semple RK;Frayling T;Perry JR;Dermitzakis E;McCarthy MI;Barroso I;Wareham NJ;Savage DB;Langenberg C;O'Rahilly S;Scott RA
通讯作者：
Scott RA
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
30.8
作者：
Mahajan A;Taliun D;Thurner M;Robertson NR;Torres JM;Rayner NW;Payne AJ;Steinthorsdottir V;Scott RA;Grarup N;Cook JP;Schmidt EM;Wuttke M;Sarnowski C;Mägi R;Nano J;Gieger C;Trompet S;Lecoeur C;Preuss MH;Prins BP;Guo X;Bielak LF;Below JE;Bowden DW;Chambers JC;Kim YJ;Ng MCY;Petty LE;Sim X;Zhang W;Bennett AJ;Bork-Jensen J;Brummett CM;Canouil M;Ec Kardt KU;Fischer K;Kardia SLR;Kronenberg F;Läll K;Liu CT;Locke AE;Luan J;Ntalla I;Nylander V;Schönherr S;Schurmann C;Yengo L;Bottinger EP;Brandslund I;Christensen C;Dedoussis G;Florez JC;Ford I;Franco OH;Frayling TM;Giedraitis V;Hackinger S;Hattersley AT;Herder C;Ikram MA;Ingelsson M;Jørgensen ME;Jørgensen T;Kriebel J;Kuusisto J;Ligthart S;Lindgren CM;Linneberg A;Lyssenko V;Mamakou V;Meitinger T;Mohlke KL;Morris AD;Nadkarni G;Pankow JS;Peters A;Sattar N;Stančáková A;Strauch K;Taylor KD;Thorand B;Thorleifsson G;Thorsteinsdottir U;Tuomilehto J;Witte DR;Dupuis J;Peyser PA;Zeggini E;Loos RJF;Froguel P;Ingelsson E;Lind L;Groop L;Laakso M;Collins FS;Jukema JW;Palmer CNA;Grallert H;Metspalu A;Dehghan A;Köttgen A;Abecasis GR;Meigs JB;Rotter JI;Marchini J;Pedersen O;Hansen T;Langenberg C;Wareham NJ;Stefansson K;Gloyn AL;Morris AP;Boehnke M;McCarthy MI
通讯作者：
McCarthy MI
影响因子：
30.8
作者：
Nelson, Christopher P.;Goel, Anuj;Deloukas, Panos
通讯作者：
Deloukas, Panos