背景:先前的研究强调了血细胞计数与慢性肝病之间的相关性。尽管如此,因果关系仍然未知。
目的:评估血细胞性状对肝酶和非酒精性脂肪性肝病(NAFLD)风险的因果关系。
方法:从血细胞联盟进行的全基因组关联研究(GWAS)中提取与血细胞性状强相关的独立遗传变异。从英国生物银行获得肝酶的汇总水平数据。NAFLD数据来自GWAS荟萃分析(8434例和770180例对照,发现数据集)和FingenGWAS(2275例和372727例对照,复制数据集)。这项分析是使用逆方差加权方法进行的,其次是各种敏感性分析。
结果:基因预测的血红蛋白浓度(HGB)的一个SD增加与0.0078的β相关(95CI:0.0059-0.0096),0.0108(95CI:0.0080-0.0136),0.0361(95CI:0.0156-0.0567),碱性磷酸酶(ALP)和0.0083(95CI:00046-0.0121),丙氨酸氨基转移酶(ALT),天冬氨酸转氨酶,和γ-谷氨酰转移酶,分别。遗传预测的血细胞比容与ALP(β=0.0078,95CI:0.0052-0.0104)和ALT(β=0.0057,95CI:0.0039-0.0075)相关。遗传测定的HGB和红细胞网织红细胞分数增加了NAFLD的风险[比值比(OR)=1.199,95CI:1.087-1.322]和(OR=1.157,95CI:1.071-1.250)。敏感性分析的结果仍然很重要。
结论:通过孟德尔随机化分析揭示了与肝酶和NAFLD发展相关的新的因果血细胞特征,这可能有助于NAFLD的诊断和预防。
BACKGROUND: Previous research has highlighted correlations between blood cell counts and chronic liver disease. Nonetheless, the causal relationships remain unknown.
OBJECTIVE: 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.
CONCLUSIONS: 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.