维生素 D 与非酒精性脂肪性肝病：双向孟德尔随机化分析。
Vitamin D and Nonalcoholic Fatty Liver Disease: Bi-directional Mendelian Randomization Analysis.
机构信息
Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
出版信息
EBioMedicine. 2018 Feb;28:187-193. doi: 10.1016/j.ebiom.2017.12.027. Epub 2018 Jan 9.
BACKGROUND
Vitamin D deficiency is associated with nonalcoholic fatty liver disease (NAFLD) in many cross-sectional studies. However, the causality between them has not been established. We used bi-directional mendelian randomization (MR) analysis to explore the causal relationship between 25-hydroxyvitamin D [25(OH)D] and NAFLD.
METHODS
9182 participants were included from a survey in East China from 2014 to 2016. We calculated weighted genetic risk scores (GRS) for 25(OH)D concentration and NAFLD based on 25(OH)D-related and NAFLD-related single nucleotide polymorphisms. Presence of liver steatosis was assessed using ultrasound. Instrumental variable was used to measure the causal relationship between them.
RESULTS
An SD increase in the 25(OH)D GRS was significantly associated with 25(OH)D (β 1.29, 95%CI -1.54, -1.04, P<0.05) but not with NAFLD (OR 0.97, 95%CI 0.92, 1.01). An SD increase in NAFLD GRS was also strongly associated with NAFLD (OR 1.09, 95%CI 1.04, 1.15, P<0.05) but not with 25(OH)D (β -0.15, 95%CI -0.41, 0.10). Using an instrumental variable estimator, no associations were found for genetically instrumented 25(OH)D with NAFLD and for genetically instrumented NAFLD with 25(OH)D.
CONCLUSION
Our results support the conclusion that there is no causal association between vitamin D and NAFLD using a bi-directional MR approach in a Chinese population.
背景
许多横断面研究表明，维生素 D 缺乏与非酒精性脂肪性肝病（NAFLD）有关。然而，它们之间的因果关系尚未确定。我们使用双向孟德尔随机化（MR）分析来探讨 25-羟维生素 D [25（OH）D]与 NAFLD 之间的因果关系。
方法
2014 年至 2016 年，我们从华东地区的一项调查中纳入了 9182 名参与者。我们根据与 25（OH）D 相关和 NAFLD 相关的单核苷酸多态性计算了 25（OH）D 浓度和 NAFLD 的加权遗传风险评分（GRS）。使用超声评估肝脂肪变性的存在。采用工具变量法来衡量它们之间的因果关系。
结果
25（OH）D GRS 每增加一个标准差，与 25（OH）D 显著相关（β 1.29，95%CI -1.54，-1.04，P<0.05），但与 NAFLD 无关（OR 0.97，95%CI 0.92，1.01）。NAFLD GRS 每增加一个标准差，与 NAFLD 也密切相关（OR 1.09，95%CI 1.04，1.15，P<0.05），但与 25（OH）D 无关（β -0.15，95%CI -0.41，0.10）。使用工具变量估计器，未发现遗传上与 25（OH）D 相关的 25（OH）D 与遗传上与 NAFLD 相关的 NAFLD 之间存在关联。
结论
使用中国人群的双向 MR 方法，我们的结果支持维生素 D 与 NAFLD 之间没有因果关系的结论。
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