Assessing causal relationships between sarcopenia and nonalcoholic fatty liver disease: A bidirectional Mendelian randomization study.
Assessing causal relationships between sarcopenia and nonalcoholic fatty liver disease: A bidirectional Mendelian randomization study.
复制标题
DOI：
10.3389/fnut.2022.971913
复制
发表时间：
2022
影响因子：
5
通讯作者：
Wang, Kai
中科院分区：
文献类型：
--
作者：
Zhao, Ze-Hua;Zou, Juanjuan;Huang, Xin;Fan, Yu-Chen;Wang, Kai
关键词：
肌肉减少症已被证明与非酒精性脂肪性肝病（NAFLD）密切相关。然而，肌肉减少症和NAFLD之间是否存在因果关系仍不确定。在这里，我们的目标是解决这个问题，使用双样本双向孟德尔随机化（MR）分析方法。我们使用来自全基因组关联研究（GWAS）的总结水平数据进行了一项双样本双向MR研究，其中包括全身瘦体重（n = 38，292），四肢（手臂和腿部）瘦体重（n = 28，330）和NAFLD（1，483例活检证实的NAFLD病例和17，781例对照）。我们首先进行了MR分析，用5个单核苷酸多态性（SNP）作为全身瘦体重的遗传工具，用3个SNP作为非全身瘦体重的遗传工具，用逆方差加权（IVW）方法估计遗传预测的肌肉减少症对NAFLD风险的因果影响。然后，我们进行了反向MR分析与四个单核苷酸多态性作为工具，以检查遗传预测的NAFLD与全身瘦体重和非全身瘦体重的因果关系。进一步进行敏感性分析，以证明MR结果的可靠性。全身瘦体重减少的遗传易感性与NAFLD无关[IVW-随机效应，比值比（OR）= 1.054，95%CI：0.750-1.482，P = 0.761]。采用遗传工具测量非肥胖人群的瘦体重也得到了相似的结果（IVW-随机效应，OR = 0.888，95%CI：0.386-2.042，P = 0.780）。反向MR分析显示，使用四种遗传工具进行遗传预测的NAFLD与全身瘦体重（IVW，β = −0.068，95%CI：−0.179至0.043，P = 0.229）和非肥胖瘦体重（IVW，β = −0.020，95%CI：−0.092至0.051，P = 0.574）无关。使用其他方法的MR分析和敏感性分析显示了一致的结果。这些结果表明，肌肉减少症和NAFLD之间没有因果关系，表明肌肉减少症可能不直接参与NAFLD的发病机制，反之亦然。
Sarcopenia has been demonstrated to be closely associated with nonalcoholic fatty liver disease (NAFLD). However, whether there are causal relationships between sarcopenia and NAFLD remains undetermined. Here, we aim to address the question using a two-sample bidirectional Mendelian randomization (MR) analysis approach. We performed a two-sample bidirectional MR study using summary-level data from genome-wide association studies (GWAS) of the whole body lean mass (n = 38,292), appendicular (arms and legs) lean mass (n = 28,330), and NAFLD (1,483 biopsy-proven NAFLD cases and 17,781 controls). We first conducted MR analysis with five single nucleotide polymorphisms (SNPs) as genetic instruments for whole body lean mass and three SNPs as instruments for appendicular lean mass to estimate the causal effect of genetically predicted sarcopenia on the risk of NAFLD using the inverse-variance weighted (IVW) method. Then we performed reverse MR analysis with four SNPs as instruments to examine the causality of genetically predicted NAFLD with whole body lean mass and appendicular lean mass. Further sensitivity analysis was conducted to testify the reliability of the MR results. Genetic predisposition to decreased whole body lean mass was not associated with NAFLD [IVW-random effects, odds ratio (OR) = 1.054, 95%CI: 0.750–1.482, P = 0.761]. Similar results were observed using genetic instruments of appendicular lean mass (IVW-random effects, OR = 0.888, 95%CI: 0.386–2.042, P = 0.780). Reverse MR analysis revealed that genetically predicted NAFLD using four genetic instruments was not associated with whole body lean mass (IVW, β = −0.068, 95%CI: −0.179 to 0.043, P = 0.229) and appendicular lean mass (IVW, β = −0.020, 95%CI: −0.092 to 0.051, P = 0.574). MR analyses using other methods and sensitivity analysis showed consistent results. These results suggested no causal relationships between sarcopenia and NAFLD, indicating that sarcopenia may not be directly involved in the pathogenesis of NAFLD and vice versa.
登录
查看更多内容
携带 patatin 样磷脂酶 3 基因变体的人类脂肪肝与胰岛素抵抗之间的关联。
影响因子：
7.7
作者：
Kantartzis K;Peter A;Machicao F;Machann J;Wagner S;Königsrainer I;Königsrainer A;Schick F;Fritsche A;Häring HU;Stefan N
通讯作者：
Stefan N
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
DOI：
10.1097/ede.0000000000000559
发表时间：
2017-01
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Burgess S;Bowden J;Fall T;Ingelsson E;Thompson SG
通讯作者：
Thompson SG
影响因子：
12.6
作者：
Hsieh, Yun-Cheng;Joo, Sae Kyung;Kim, Won
通讯作者：
Kim, Won
影响因子：
25.7
作者：
Lee, Yong-ho;Jung, Kyu Sik;Cha, Bong-Soo
通讯作者：
Cha, Bong-Soo