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 ...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 aβof 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 gammaglutamyl 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.展开更多
Wilson's disease(WD),also called hepatolenticular degeneration,is an autosomal recessive copper dysfunction disorder that is among the few treatable neurogenetic disorders.The main goals for controlling WD are to ...Wilson's disease(WD),also called hepatolenticular degeneration,is an autosomal recessive copper dysfunction disorder that is among the few treatable neurogenetic disorders.The main goals for controlling WD are to lower copper intake and encourage copper removal.Medical treatments and low-copper diets are available,but many problems remain.For example,the current treatments cannot fix copper metabolism and are unable to cross the blood-brain barrier.Furthermore,severe side effects have been experienced by many patients with WD.Because lifelong therapy is required for this disease,adherence to medical therapy and best practices for monitoring and personalizing therapy continue to evolve;some of these issues are being addressed in ongoing studies.Additionally,novel chelating agents,gene therapies using adeno-associated viruses,and variant-specific therapies that may improve neurological outcomes are in development.Here,we review the latest treatment innovations that may play an essential role for patients with WD in the future.展开更多
基金the Shanghai Natural Science Foundation of China,No.23ZR1447800and the Fengxian District Science and Technology Commission Project,China,No.20211838.
文摘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 aβof 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 gammaglutamyl 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.
基金supported by the research foundation(188020–193810101/089)for distinguished scholar of Zhejiang University to Zhi-Ying Wu.
文摘Wilson's disease(WD),also called hepatolenticular degeneration,is an autosomal recessive copper dysfunction disorder that is among the few treatable neurogenetic disorders.The main goals for controlling WD are to lower copper intake and encourage copper removal.Medical treatments and low-copper diets are available,but many problems remain.For example,the current treatments cannot fix copper metabolism and are unable to cross the blood-brain barrier.Furthermore,severe side effects have been experienced by many patients with WD.Because lifelong therapy is required for this disease,adherence to medical therapy and best practices for monitoring and personalizing therapy continue to evolve;some of these issues are being addressed in ongoing studies.Additionally,novel chelating agents,gene therapies using adeno-associated viruses,and variant-specific therapies that may improve neurological outcomes are in development.Here,we review the latest treatment innovations that may play an essential role for patients with WD in the future.
