8 research outputs found
Comparison of the Lipidomic Signature of Fatty Liver in Children and Adults: A Cross-Sectional Study.
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an increasingly common condition in children characterised by insulin resistance and altered lipid metabolism. Affected patients are at increased risk of cardiovascular disease (CVD) and children with NAFLD are likely to be at risk of premature cardiac events. Evaluation of the plasma lipid profile of children with NAFLD offers the opportunity to investigate these perturbations and understand how closely they mimic the changes seen in adults with cardiometabolic disease. METHODS: We performed untargeted liquid chromatography-mass spectrometry (LC-MS) plasma lipidomics on 287 children: 19 lean controls, 146 from an obese cohort, and 122 NAFLD cases who had undergone liver biopsy. Associations between lipid species and liver histology were assessed using regression adjusted for age and sex. Results were then replicated using data from 9500 adults with metabolic phenotyping. RESULTS: More severe paediatric NAFLD was associated with lower levels of long chain, polyunsaturated phosphatidylcholines (pC) and triglycerides (TG). Similar trends in pC and TG chain length and saturation were seen in adults with hepatic steatosis; however, many of the specific lipids associated with NAFLD differed between children and adults. Five lipids replicated in adults (including PC(36:4)) have been directly linked to death and cardiometabolic disease, as well as indirectly via genetic variants. CONCLUSION: These findings suggest that, whilst similar pathways of lipid metabolism are perturbed in paediatric NAFLD as in cardiometabolic disease in adults, the specific lipid signature in children is different.JPM is supported by a Wellcome Trust fellowship (216329/Z/19/Z), a European Society for Paediatric Research (ESPR) Young Investigator Award, and a Childrenâs Liver Disease Foundation Grant. EU-PNAFLD Registry is supported by a European Association for Study of the Liver (EASL) Registry Grant. MZ is supported by a New Investigator Research Grant from the MRC (MR/T001917/1). BK is supported by grants from Van den Broek Lohman Foundation, Virtutis Opus Foundation and For Wishdom Foundation. SF, SGS & AK are supported by the BBSRC (BB/M027252/1 & BB/P028195/1), BJJ & AK are supported by the National Institute for Health Research (NIHR146281)
rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD : A meta-analysis
Publisher Copyright: © 2020 European Association for the Study of the Liver Funding text 1 J.P.M. is supported by a Wellcome Trust Fellowship ( 216329/Z/19/Z ), a European Paediatric Research Society award and a Children's Liver Disease Foundation grant. The EU-PNAFLD is supported by an EASL Registry Grant . NIH grants: R01HD028016 (S.C.), R01DK111038 (S.C)., R01DK114504 (N.S.), DK091601 (J.K.D.) and UL1TR001105 (J.K.). Supported by the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) ( U01DK061718 , U01DK061728 , U01DK061731 , U01DK061732 , U01DK061734 , U01DK061737 , U01DK061738 , U01DK061730 , and U01DK061713 ); the National Center for Advancing Translational Sciences ( UL1TR000439 , UL1TR000436 , UL1TR000006 , UL1TR000448 , UL1TR000100 , UL1TR000004 , UL1TR000423 , UL1TR000058 , and UL1TR001881 ); and the NIDDK ( DK063491 to the Southern California Diabetes Endocrinology Research Center). This study was supported by the German Federal Ministry for Education and Research (BmBF) through the Livers Systems Medicine (LiSyM) project. This work was supported by grants from the Swiss National Funds (SNF no. 310030_169196 ) and the Swiss Foundation for Alcohol Research (SSA) to F.S. This Raine Study was supported by the National Health and Medical Research Council of Australia (grant numbers 403981 , 353514 and 572613 ). The UK Medical Research Council and Wellcome (grant ref: 102215/2/13/2 ) and the University of Bristol provide core support for ALSPAC. ALSPAC GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe . A comprehensive list of grants funding is available on the ALSPAC website ( www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ); this research was specifically funded by grants from MRC and Alcohol Research UK ( MR/L022206/1 ) and NIH ( 5R01AA018333-05 ) to K.W.M.A. and M.H. L.V. was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358 , Ricerca corrente Fondazione IRCCS Caâ Granda Ospedale Maggiore Policlinico . German Federal Ministry of Education and Research (BMBF LiSyM 031L0051 to F.L.). P.L. is supported by grants from the Sigrid JusĂ©lius Foundation and the Novo Nordisk Foundation . The Fenland study was funded by grants to the MRC Epidemiology Unit ( MC UU12015/1 , MC UU 12015/5 ). R.B. and M.K. are employees of and shareholders in Perspectum Diagnostics Ltd. C.A.P. is funded by a Wellcome Trust Clinical PhD Programme ( 206274/Z/17/Z ). J.M.B. is supported by the Spanish Carlos III Health Institute (ISCIII; PI15/01132 , PI18/01075 , CIBERehd, and Miguel Servet Program CON14/00129) co-financed by Fondo Europeo de Desarrollo Regional (FEDER) and La Caixa Scientific Foundation ( HR17-00601 ). Research from the GUARDIAN Study was supported DK085175 and DK118062, and phenotyping in IRASFS was supported by HL060944, HL061019, HL060919 and HL060894 IRASFS from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). H.Y. is funded by a Diabetes UK RD Lawrence fellowship ( 17/0005594 ). Q.M.A. and A.D. supported by the EPoS (Elucidating Pathways of Steatohepatitis) consortium funded by the Horizon 2020 Framework Program of the European Union under Grant Agreement 634413 . Q.M.A., A.D., L.V. and A.G. are members of the LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis) consortium funded by the European Union Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under grant agreement 777377. Q.M.A. is a Newcastle NIHR Biomedical Research Center Investigator. Funding text 2 J.P.M. is supported by a Wellcome Trust Fellowship (216329/Z/19/Z), a European Paediatric Research Society award and a Children's Liver Disease Foundation grant. The EU-PNAFLD is supported by an EASL Registry Grant. NIH grants: R01HD028016 (S.C.), R01DK111038 (S.C)., R01DK114504 (N.S.), DK091601 (J.K.D.) and UL1TR001105 (J.K.). Supported by the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, and U01DK061713); the National Center for Advancing Translational Sciences (UL1TR000439, UL1TR000436, UL1TR000006, UL1TR000448, UL1TR000100, UL1TR000004, UL1TR000423, UL1TR000058, and UL1TR001881); and the NIDDK (DK063491 to the Southern California Diabetes Endocrinology Research Center). This study was supported by the German Federal Ministry for Education and Research (BmBF) through the Livers Systems Medicine (LiSyM) project. This work was supported by grants from the Swiss National Funds (SNF no. 310030_169196) and the Swiss Foundation for Alcohol Research (SSA) to F.S. This Raine Study was supported by the National Health and Medical Research Council of Australia (grant numbers 403981, 353514 and 572613). The UK Medical Research Council and Wellcome (grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. ALSPAC GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. A comprehensive list of grants funding is available on the ALSPAC website (www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf); this research was specifically funded by grants from MRC and Alcohol Research UK (MR/L022206/1) and NIH (5R01AA018333-05) to K.W.M.A. and M.H. L.V. was supported by MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca? Granda Ospedale Maggiore Policlinico. German Federal Ministry of Education and Research (BMBF LiSyM 031L0051 to F.L.). P.L. is supported by grants from the Sigrid Jus?lius Foundation and the Novo Nordisk Foundation. The Fenland study was funded by grants to the MRC Epidemiology Unit (MC UU12015/1, MC UU 12015/5). R.B. and M.K. are employees of and shareholders in Perspectum Diagnostics Ltd. C.A.P. is funded by a Wellcome Trust Clinical PhD Programme (206274/Z/17/Z). J.M.B. is supported by the Spanish Carlos III Health Institute (ISCIII; PI15/01132, PI18/01075, CIBERehd, and Miguel Servet Program CON14/00129) co-financed by Fondo Europeo de Desarrollo Regional (FEDER) and La Caixa Scientific Foundation (HR17-00601). Research from the GUARDIAN Study was supported DK085175 and DK118062, and phenotyping in IRASFS was supported by HL060944, HL061019, HL060919 and HL060894 IRASFS from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). H.Y. is funded by a Diabetes UK RD Lawrence fellowship (17/0005594). Q.M.A. and A.D. supported by the EPoS (Elucidating Pathways of Steatohepatitis) consortium funded by the Horizon 2020 Framework Program of the European Union under Grant Agreement 634413. Q.M.A., A.D., L.V. and A.G. are members of the LITMUS (Liver Investigation: Testing Biomarker Utility in Steatohepatitis) consortium funded by the European Union Innovative Medicines Initiative 2 (IMI2) Joint Undertaking under grant agreement 777377. Q.M.A. is a Newcastle NIHR Biomedical Research Center Investigator. Funding text 3 The authors are grateful to the Raine Study participants and their families, and to the Raine Study research staff for cohort coordination and data collection. The authors gratefully acknowledge the following institutes for providing funding for Core Management of the Raine Study: The University of Western Australia (UWA), Curtin University, the Raine Medical Research Foundation, the UWA Faculty of Medicine, Dentistry and Health Sciences, the Telethon Kids Institute, the Women and Infants Research Foundation (King Edward Memorial Hospital), and Edith Cowan University). We are extremely grateful to all the families who took part in the ALSPAC study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, and nurses. This study was conducted using data from the Fenland study. The authors gratefully acknowledge the help of the MRC Epidemiology Unit Support Teams, including Field, Laboratory, and Data Management Teams. The authors are grateful to the members of the EU-PNAFLD Registry, including Anita Vreugdenhil, Anna Alisi, Piotr Socha, Wojciech JaĆczyk, Ulrich Baumann, Sanjay Rajwal, Indra van Mourik, Florence Lacaille, Myriam Dabbas, Deirdre A. Kelly, and the late Valerio Nobili. The authors are also grateful to the members of the GOLD consortium: Gudny Eiriksdottir, Melissa E. Garcia, Vilmundur Gudnason, Tamara B. Harris, Lauren J. Kim, Lenore J. Launer, Michael A. Nalls, Albert V. Smith,Jeanne M. Clark, Ruben Hernaez, W. H. Linda Kao, Braxton D. Mitchell, Alan R. Shuldiner, Laura M. Yerges-Armstrong, Ingrid B. Borecki, J. Jeffrey Carr, Mary F. Feitosa, Jun Wu, Johannah L. Butler, Caroline S. Fox, Joel N. Hirschhorn, Udo Hoffmann, Shih-Jen Hwang, Joseph M. Massaro, Christopher J. O'Donnell, Cameron D. Palmer, Dushyant V. Sahani, Elizabeth K. Speliotes. We would also like to thank Naga Chalasani for his helpful comments. This research made use of the UK Biobank resource under project number 9914.Background & Aims: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis. Methods: We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models. Results: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02â0.05], pz = 4.8Ă10â5) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05â1.3], pz = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03â1.45], pz = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz = 0.002) and lower serum triglycerides (pz = 1.5Ă10â4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD. Conclusions: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent. Lay summary: Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including âcirrhosisâ). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change (âvariantâ) in one gene (âMBOAT7â) was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.Peer reviewe
rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD : A meta-analysis
Background & Aims: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis. Methods: We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models. Results: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02-0.05], p(z) = 4.8x10(-5)) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05-1.3], p(z) = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03-1.45], p(z) = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (p(z) = 0.002) and lower serum triglycerides (p(z) = 1.5x10(-4)). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD. Conclusions: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent. Lay summary: Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including 'cirrhosis'). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change ('variant') in one gene ('MBOAT7') was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease. (C) 2020 European Association for the Study of the Liver. Published by Elsevier B.V.Peer reviewe
Variants in mitochondrial amidoxime reducing component 1 and hydroxysteroid 17-beta dehydrogenase 13 reduce severity of nonalcoholic fatty liver disease in children and suppress fibrotic pathways through distinct mechanisms.
Funder: Childrenâs Liver Disease Foundation; Id: http://dx.doi.org/10.13039/501100000290Funder: European Society for Paediatric Research; Id: http://dx.doi.org/10.13039/501100008873Funder: Virtutis Opus FoundationFunder: European Association for the Study of the Liver; Id: http://dx.doi.org/10.13039/501100009253Funder: For Wishdom FoundationFunder: Italian Ministry of HealthFunder: Van den Broek Lohman FoundationGenome-wide association studies in adults have identified variants in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) and mitochondrial amidoxime reducing component 1 (MTARC1) as protective against nonalcoholic fatty liver disease (NAFLD). We aimed to test their association with pediatric NAFLD liver histology and investigate their function using metabolomics. A total of 1450 children (729 with NAFLD, 399 with liver histology) were genotyped for rs72613567T>TA in HSD17B13, rs2642438G>A in MTARC1, and rs738409C>G in patatin-like phospholipase domain-containing protein 3 (PNPLA3). Genotype-histology associations were tested using ordinal regression. Untargeted hepatic proteomics and plasma lipidomics were performed in a subset of children. We found rs72613567T>TA in HSD17B13 to be associated with lower odds of NAFLD diagnosis (odds ratio, 0.7; 95% confidence interval, 0.6-0.9) and a lower grade of portal inflammation (p A in MTARC1 was associated with a lower grade of hepatic steatosis (p = 0.02). Proteomics found reduced expression of HSD17B13 in carriers of the protective -TA allele. MTARC1 levels were unaffected by genotype. Both variants were associated with down-regulation of fibrogenic pathways. HSD17B13 perturbs plasma phosphatidylcholines and triglycerides. In silico modeling suggested p.Ala165Thr disrupts the stability and metal binding of MTARC1. Conclusion: Both HSD17B13 and MTARC1 variants are associated with less severe pediatric NAFLD. These results provide further evidence for shared genetic mechanisms between pediatric and adult NAFLD
rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD: a meta-analysis
Background & aims: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.
Methods: We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.
Results: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10-5) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.
Conclusion: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent
rs641738C>T near MBOAT7 is associated with liver fat, ALT and fibrosis in NAFLD: A meta-analysis.
BACKGROUND & AIMS: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis. METHODS: We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models. RESULTS: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02-0.05], pz = 4.8Ă10-5) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05-1.3], pz = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03-1.45], pz = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz = 0.002) and lower serum triglycerides (pz = 1.5Ă10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD. CONCLUSIONS: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent. LAY SUMMARY: Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including 'cirrhosis'). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change ('variant') in one gene ('MBOAT7') was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease.JPM is supported by a Wellcome Trust Fellowship (216329/Z/19/Z
rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD : a meta-analysis
Background & Aims: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in NAFLD; however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and to characterise its role in the regulation of related metabolic phenotypes through a meta-analysis. Methods: We performed a meta-analysis of studies with data on the association between rs641738C>T genotype and liver fat, NAFLD histology, and serum alanine aminotransferase (ALT), lipids or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed a random effects meta-analysis using recessive, additive and dominant genetic models. Results: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI 0.02\u20130.05], pz = 4.8
710\u20135) and diagnosis of NAFLD (odds ratio [OR] 1.17 [95% CI 1.05\u20131.3], pz = 0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI 1.03\u20131.45], pz = 0.021) in Caucasian adults using a recessive model of inheritance (CC + CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz = 0.002) and lower serum triglycerides (pz = 1.5
710\u20134). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD. Conclusions: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent. Lay summary: Fatty liver disease is a common condition where fat builds up in the liver, which can cause liver inflammation and scarring (including \u2018cirrhosis\u2019). It is closely linked to obesity and diabetes, but some genes are also thought to be important. We did this study to see whether one specific change (\u2018variant\u2019) in one gene (\u2018MBOAT7\u2019) was linked to fatty liver disease. We took data from over 40 published studies and found that this variant near MBOAT7 is linked to more severe fatty liver disease. This means that drugs designed to work on MBOAT7 could be useful for treating fatty liver disease