血细胞计数与非酒精性脂肪肝:孟德尔随机分析的证据。

IF 2.5 Q2 GASTROENTEROLOGY & HEPATOLOGY
Bin Hu, Ai-Hong Wan, Xi-Qiao Xiang, Yuan-Hao Wei, Yi Chen, Zhen Tang, Chang-De Xu, Zi-Wei Zheng, Shao-Ling Yang, Kun Zhao
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引用次数: 0

摘要

背景:以往的研究强调了血细胞计数与慢性肝病之间的相关性。目的:评估血细胞特质对肝酶和非酒精性脂肪肝(NAFLD)风险的因果效应:方法:从血细胞联盟开展的全基因组关联研究(GWAS)中提取与血细胞特质密切相关的独立遗传变异。肝酶的汇总数据来自英国生物库。非酒精性脂肪肝数据来自一项GWAS荟萃分析(83434例病例和770180例对照,发现数据集)和芬根GWAS(2275例病例和372727例对照,复制数据集)。该分析采用了逆方差加权法,然后进行了各种敏感性分析:结果:遗传预测血红蛋白浓度(HGB)每增加 1 SD,β值分别为 0.0078(95%CI:0.0059-0.0096)、0.0108(95%CI:0.0080-0.0136)、0.0361(95%CI:0.0156-0.0567),碱性磷酸酶(ALP)、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶和γ-谷氨酰转移酶分别为 0.0083(95%CI:00046-0.0121)。基因预测的血细胞比容与 ALP(β = 0.0078,95%CI:0.0052-0.0104)和 ALT(β = 0.0057,95%CI:0.0039-0.0075)相关。由基因决定的 HGB 和红细胞网织红细胞比例会增加非酒精性脂肪肝的风险[比值比 (OR) = 1.199,95%CI:1.087-1.322]和(OR = 1.157,95%CI:1.071-1.250)。敏感性分析的结果仍然显著:结论:通过孟德尔随机分析发现了与肝酶和非酒精性脂肪肝发展相关的新的血细胞因果性状,这可能有助于非酒精性脂肪肝的诊断和预防。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Blood cell counts and nonalcoholic fatty liver disease: Evidence from Mendelian randomization analysis.

Background: Previous research has highlighted correlations between blood cell counts and chronic liver disease. Nonetheless, the causal relationships remain unknown.

Aim: To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease (NAFLD) risk.

Methods: Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study (GWAS) conducted by the Blood Cell Consortium. Summary-level data for liver enzymes were obtained from the United Kingdom Biobank. NAFLD data were obtained from a GWAS meta-analysis (8434 cases and 770180 controls, discovery dataset) and the Fingen GWAS (2275 cases and 372727 controls, replication dataset). This analysis was conducted using the inverse-variance weighted method, followed by various sensitivity analyses.

Results: One SD increase in the genetically predicted haemoglobin concentration (HGB) was associated with a β of 0.0078 (95%CI: 0.0059-0.0096), 0.0108 (95%CI: 0.0080-0.0136), 0.0361 (95%CI: 0.0156-0.0567), and 0.0083 (95%CI: 00046-0.0121) for alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transferase, respectively. Genetically predicted haematocrit was associated with ALP (β = 0.0078, 95%CI: 0.0052-0.0104) and ALT (β = 0.0057, 95%CI: 0.0039-0.0075). Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD [odds ratio (OR) = 1.199, 95%CI: 1.087-1.322] and (OR = 1.157, 95%CI: 1.071-1.250). The results of the sensitivity analyses remained significant.

Conclusion: Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis, which may facilitate the diagnosis and prevention of NAFLD.

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来源期刊
World Journal of Hepatology
World Journal of Hepatology GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
4.10
自引率
4.20%
发文量
172
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