Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease: Mendelian randomization and meta-analysis of 279 013 individuals

European Heart Journal

Volumn 39, Issue 5, 2018, Pages 385-393

  Lauridsen, Bo Kobberø ^a,b   Stender, Stefan ^a,b   Kristensen, Thomas Skårup ^a,b   Kofoed, Klaus Fuglsang ^a,b   Køber, Lars ^a,b   Nordestgaard, Børge G ^b,c,d   Tybjærg Hansen, Anne ^a,b,c,d  

^a Rigshospitalet   (Denmark)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c GENTOFTE UNIVERSITY HOSPITAL   (Denmark)

^d FREDERIKSBERG HOSPITAL   (Denmark)

Author keywords

Cardiovascular disease; Causality; Epidemiology; Genetics; Liver disease

Indexed keywords

AGED; COHORT ANALYSIS; COMPLICATION; DENMARK; FEMALE; GENETICS; HEART MUSCLE ISCHEMIA; HUMAN; LIVER; MALE; MENDELIAN RANDOMIZATION ANALYSIS; META ANALYSIS; MIDDLE AGED; NONALCOHOLIC FATTY LIVER; PATHOLOGY; RISK FACTOR;

AGED; COHORT STUDIES; DENMARK; FEMALE; HUMANS; LIVER; MALE; MENDELIAN RANDOMIZATION ANALYSIS; MIDDLE AGED; MYOCARDIAL ISCHEMIA; NON-ALCOHOLIC FATTY LIVER DISEASE; RISK FACTORS;

EID: 85044116085     PISSN: 0195668X     EISSN: 15229645     Source Type: Journal    
DOI: 10.1093/eurheartj/ehx662     Document Type: Article

References (30)

1. Caballeria L, Pera G, Auladell MA, Toran P, Munoz L, Miranda D, Aluma A, Casas JD, Sanchez C, Gil D, Auba J, Tibau A, Canut S, Bernad J, Aizpurua MM. Prevalence and factors associated with the presence of nonalcoholic fatty liver disease in an adult population in Spain. Eur J Gastroenterol Hepatol 2010; 22:24-32.
2. van den Berg EH, Amini M, Schreuder TCMA, Dullaart RPF, Faber KN, Alizadeh BZ, Blokzijl H, Petta S. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: a large Dutch population cohort. PLoS One 2017; 12:e0171502.
3. Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, Ahmed A. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology 2015; 148:547-555.
4. Lonardo A, Sookoian S, Pirola CJ, Targher G. Non-alcoholic fatty liver disease and risk of cardiovascular disease. Metabolism 2016; 65:1136-1150.
5. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 2010; 363:1341-1350.
6. Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey SG. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 2008; 27:1133-1163.
7. Swerdlow DI, Kuchenbaecker KB, Shah S, Sofat R, Holmes MV, White J, Mindell JS, Kivimaki M, Brunner EJ, Whittaker JC, Casas JP, Hingorani AD. Selecting instruments for Mendelian randomization in the wake of genome-wide association studies. Int J Epidemiol 2016; 45:1600-1616.
8. Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, Boerwinkle E, Cohen JC, Hobbs HH. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40:1461-1465.
9. Smagris E, BasuRay S, Li J, Huang Y, Lai KM, Gromada J, Cohen JC, Hobbs HH. Pnpla3I148M knockin mice accumulate PNPLA3 on lipid droplets and develop hepatic steatosis. Hepatology 2015; 61:108-118.
10. Kozlitina J, Smagris E, Stender S, Nordestgaard BG, Zhou HH, Tybjærg-Hansen A, Vogt TF, Hobbs HH, Cohen JC. Exome-wide association study identifies a TM6SF2 variant that confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2014; 46:352-356.
11. Pickhardt PJ, Park SH, Hahn L, Lee SG, Bae KT, Yu ES. Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: implications for the investigation of the natural history of incidental steatosis. Eur Radiol 2012; 22:1075-1082.
12. Kodama Y, Ng CS, Wu TT, Ayers GD, Curley SA, Abdalla EK, Vauthey JN, Charnsangavej C. Comparison of CT methods for determining the fat content of the liver. AJR Am J Roentgenol 2007; 188:1307-1312.
13. Yajima Y, Narui T, Ishii M, Abe R, Ohtsuki M, Goto Y, Endo S, Yamada K, Ito M. Computed tomography in the diagnosis of fatty liver: total lipid content and computed tomography number. Tohoku J Exp Med 1982; 136:337-342.
14. Speliotes EK, Yerges-Armstrong LM, Wu J, Hernaez R, Kim LJ, Palmer CD, Gudnason V, Eiriksdottir G, Garcia ME, Launer LJ, Nalls MA, Clark JM, Mitchell BD, Shuldiner AR, Butler JL, Tomas M, Hoffmann U, Hwang S-J, Massaro JM, O'Donnell CJ, Sahani DV, Salomaa V, Schadt EE, Schwartz SM, Siscovick DS, Voight BF, Carr JJ, Feitosa MF, Harris TB, Fox CS, Smith AV, Kao WHL, Hirschhorn JN, Borecki IB, McCarthy MI; GOLD Consortium. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet 2011; 7:e10001324.
15. Tang CS, Zhang H, Cheung CY, Xu M, Ho JC, Zhou W, Cherny SS, Zhang Y, Holmen O, Au KW, Yu H, Xu L, Jia J, Porsch RM, Sun L, Xu W, Zheng H, Wong LY, Mu Y, Dou J, Fong CH, Wang S, Hong X, Dong L, Liao Y, Wang J, Lam LS, Su X, Yan H, Yang ML, Chen J, Siu CW, Xie G, Woo YC, Wu Y, Tan KC, Hveem K, Cheung BM, Zöllner S, Xu A, Eugene Chen Y, Jiang CQ, Zhang Y, Lam TH, Ganesh SK, Huo Y, Sham PC, Lam KS, Willer CJ, Tse HF, Gao W. Exomewide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese. Nat Commun 2015; 6:10206.
16. Chami N, Chen M-H, Slater AJ, Eicher JD, Evangelou E, Tajuddin SM, Love-Gregory L, Kacprowski T, Schick UM, Nomura A, Giri A, Lessard S, Brody JA, Schurmann C, Pankratz N, Yanek LR, Manichaikul A, Pazoki R, Mihailov E, Hill WD, Raffield LM, Burt A, Bartz TM, Becker DM, Becker LC, Boerwinkle E, Bork-Jensen J, Bottinger EP, O'Donoghue ML, Crosslin DR, de Denus S, Dubé M-P, Elliott P, Engström G, Evans MK, Floyd JS, Fornage M, Gao HE, Greinacher A, Gudnason V, Hansen T, Harris TB, Hayward C, Hernesniemi J, Highland HM, Hirschhorn JN, Hofman A, Irvin MR, Kähönen M, Lange E, Launer LJ, Lehtimäki T, Li J, Liewald DCM, Linneberg A, Liu Y, Lu Y, Lyytikäinen L-P, Mägi R, Mathias RA, Melander O, Metspalu A, Mononen N, Nalls MA, Nickerson DA, Nikus K, O'Donnell CJ, Orho-Melander M, Pedersen O, Petersmann A, Polfus L, Psaty BM, Raitakari OT, Raitoharju E, Richard M, Rice KM, Rivadeneira F, Rotter JI, Schmidt F, Smith AV, Starr JM, Taylor KD, Teumer A, Thuesen BH, Torstenson ES, Tracy RP, Tzoulaki I, Zakai NA, Vacchi-Suzzi C, van Duijn CM, van Rooij FJA, Cushman M, Deary IJ, Velez Edwards DR, Vergnaud A-C, Wallentin L, Waterworth DM, White HD, Wilson JG, Zonderman AB, Kathiresan S, Grarup N, Esko T, Loos RJF, Lange LA, Faraday N, Abumrad NA, Edwards TL, Ganesh SK, Auer PL, Johnson AD, Reiner AP, Lettre G. Exome genotyping identifies pleiotropic variants associated with red blood cell traits. Am J Hum Genet 2016; 99: 8-21.
17. CARDIoGRAMplusC4D Consortium. A comprehensive 1, 000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet 2015; 47:1121-1130.
18. Stender S, Kozlitina J, Nordestgaard BG, Tybjærg-Hansen A, Hobbs HH, Cohen JC. Adiposity amplifies the genetic risk of fatty liver disease conferred by multiple loci. Nat Genet 2017; 49:842-847.
19. Krawczyk M, Portincasa P, Lammert F. PNPLA3-associated steatohepatitis: toward a gene-based classification of fatty liver disease. Semin Liver Dis 2013; 33: 369-379.
20. Simons N, Isaacs A, Koek GH, Kuc S, Schaper NC, Brouwers MC. PNPLA3, TM6SF2, and MBOAT7 genotypes and coronary artery disease. Gastroenterology 2017; 152:912-913.
21. Marchesini G, Day CP, Dufour JF, Canbay A, Nobili V, Ratziu V, Tilg H, Roden M, Gastaldelli A, Yki-Järvinen H, Schick F, Vettor R, Frühbeck G, Mathus-Vliegen L. EASL-EASD-EASO clinical practice guidelines for the management of nonalcoholic fatty liver disease. J Hepatol 2016; 64:1388-1402.
22. Varbo A, Benn M, Tybjærg-Hansen A, Jørgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol 2013; 61:427-436.
23. Jørgensen AB, Frikke-Schmidt R, West AS, Grande P, Nordestgaard BG, Tybjærg-Hansen A. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J 2013; 34:1826-1833.
24. Nordestgaard BG Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology. Circ Res 2016; 118:547-563.
25. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, Hoes AW, Jennings CS, Landmesser U, Pedersen TR, Reiner Z, Riccardi G, Taskinen MR, Tokgozoglu L, Verschuren WM, Vlachopoulos C, Wood DA, Zamorano JL. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J 2016; 37:2999-3058.
26. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corrà U, Cosyns B, Deaton C, Graham I, Hall MS, Hobbs FD, Løchen ML, Löllgen H, Marques-Vidal P, Perk J, Prescott E, Redon J, Richter DJ, Sattar N, Smulders Y, Tiberi M, van der Worp HB, van Dis I, Verschuren WM. 2016 European guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European Society of Cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur HeartJ 2016; 37:2315-2381.
27. Holmen OL, Zhang H, Fan Y, Hovelson DH, Schmidt EM, Zhou W, Guo Y, Zhang J, Langhammer A, Lochen ML, Ganesh SK, Vatten L, Skorpen F, Dalen H, Zhang J, Pennathur S, Chen J, Platou C, Mathiesen EB, Wilsgaard T, Njolstad I, Boehnke M, Chen YE, Abecasis GR, Hveem K, Willer CJ. Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk. Nat Genet 2014; 46:345-351.
28. Pirola CJ, Sookoian S. The dual and opposite role of the TM6SF2-rs58542926 variant in protecting against cardiovascular disease and conferring risk for nonalcoholic fatty liver: a meta-analysis. Hepatology 2015; 62:1742-1756.
29. Paré G, Ridker PM, Rose L, Barbalic M, Dupuis J, Dehghan A, Bis JC, Benjamin EJ, Shiffman D, Parker AN, Chasman DI. Genome-wide association analysis of soluble ICAM-1 concentration reveals novel associations at the NFKBIK, PNPLA3; RELA, and SH2B3 loci. PLoS Genet 2011; 7:e1001374.
30. Mancina RM, Dongiovanni P, Petta S, Pingitore P, Meroni M, Rametta R, Boren J, Montalcini T, Pujia A, Wiklund O, Hindy G, Spagnuolo R, Motta BM, Pipitone RM, Craxi A, Fargion S, Nobili V, Kakela P, Karja V, Mannisto V, Pihlajamaki J, Reilly DF, Castro-Perez J, Kozlitina J, Valenti L, Romeo S. The MBOAT7-TMC4 Variant rs641738 increases risk of nonalcoholic fatty liver disease in individuals of European descent. Gastroenterology 2016; 150:1219-1230.