Yuan Shuai, Chen Jie, Vujkovic Marijana, Chang Kyong-Mi, Li Xue, Larsson Susanna C, Gill Dipender
Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Centre for Global Health, Zhejiang University School of Medicine, Hangzhou, China.
BMJ Med. 2022 Dec 20;1(1):e000277. doi: 10.1136/bmjmed-2022-000277. eCollection 2022.
To investigate the effects of metabolic traits, lifestyle factors, and drug interventions on liver fat using the mendelian randomisation paradigm.
Mendelian randomisation study.
Publicly available summary level data from genome-wide association studies.
Genome-wide association studies of 32 974 to 1 407 282 individuals who were predominantly of European descent.
Genetic variants predicting nine metabolic traits, six lifestyle factors, four lipid lowering drug targets, three antihypertensive drug targets, and genetic association estimates formagnetic resonance imaging measured liver fat.
Mendelian randomisation analysis was used to investigate the effects of these exposures on liver fat, incorporating sensitivity analyses that relaxed the requisite modelling assumptions.
Genetically predicted liability to obesity, type 2 diabetes, elevated blood pressure, elevated triglyceride levels, cigarette smoking, and sedentary time watching television were associated with higher levels of liver fat. Genetically predicted lipid lowering drug effects were not associated with liver fat; however, β blocker and calcium channel blocker antihypertensive drug effects were associated with lower levels of liver fat.
These analyses provide evidence of a causal effect of various metabolic traits, lifestyle factors, and drug targets on liver fat. The findings complement existing epidemiological associations, further provide mechanistic insight, and potentially supports a role for drug interventions in reducing the burden of hepatic steatosis and related disease. Further clinical study is now warranted to investigate the relevance of these genetic analyses for patient care.
采用孟德尔随机化范式研究代谢特征、生活方式因素和药物干预对肝脏脂肪的影响。
孟德尔随机化研究。
来自全基因组关联研究的公开汇总水平数据。
对32974至1407282名主要为欧洲血统个体进行的全基因组关联研究。
预测9种代谢特征、6种生活方式因素、4种降脂药物靶点、3种抗高血压药物靶点的基因变异，以及通过磁共振成像测量肝脏脂肪的基因关联估计值。
采用孟德尔随机化分析研究这些暴露因素对肝脏脂肪的影响，并纳入放宽必要建模假设的敏感性分析。
遗传预测的肥胖、2型糖尿病、血压升高、甘油三酯水平升高、吸烟和久坐看电视的易感性与肝脏脂肪水平较高有关。遗传预测的降脂药物作用与肝脏脂肪无关；然而，β受体阻滞剂和钙通道阻滞剂的抗高血压药物作用与较低的肝脏脂肪水平有关。
这些分析提供了各种代谢特征、生活方式因素和药物靶点对肝脏脂肪有因果作用的证据。这些发现补充了现有的流行病学关联，进一步提供了机制性见解，并可能支持药物干预在减轻肝脂肪变性和相关疾病负担方面的作用。现在有必要进行进一步的临床研究，以调查这些基因分析对患者护理的相关性。
