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Emdin, C. A. et al. A missense variant in mitochondrial amidoxime reducing comp\ onent 1 gene and protection against liver disease. PLoS Genet. 16, e1008629 \(2020\).\r:155)/F 4/H/N/Rect[199.806 377.77 205.746 367.59]/Subtype/Link/Type/Annot>> endobj 77 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:21. Abul-Husn, N. S. et al. A protein-truncating HSD17B13 variant and protection f\ rom chronic liver disease. N. Engl. J. Med. 378, 1096 1106 \(2018\).\r:156)/F 4/H/N/Rect[146.865 184.27 151.564 174.09]/Subtype/Link/Type/Annot>> endobj 78 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Table 1 | Fraction of participants with high versus low BMI and PDFF in the UKB c\ ohorts\r:157)/F 4/H/N/Rect[114.505 87.5204 118.123 77.3399]/Subtype/Link/Type/Annot>> endobj 79 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 1 | The distribution of PDFF measurements. a, Histogram of PDFF in the\ IDEAL cohort. b, Histogram of PDFF in the GRE cohort. c, PDFF plotted against BMI in the UKB IDEAL cohort \(n = 27,668\). \ d, PDFF plotted against BMI in the:158)/F 4/H/N/Rect[152.771 87.5204 156.307 77.3399]/Subtype/Link/Type/Annot>> endobj 80 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:49. Gold, L., Walker, J. J., Wilcox, S. K. & Williams, S. Advances in human proteomi\ cs at high scale with the SOMAscan proteomics platform. Nat. Biotechnol. 29, 543 549 \(2012\).\r:159)/F 4/H/N/Rect[505.966 195.02 511.868 184.84]/Subtype/Link/Type/Annot>> endobj 81 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:50. Ferkingstad, E. et al. Large-scale integration of the plasma \nproteome with gene\ tics and disease. Nat. 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PNPLA3 p.I148M variant is associated with greater reduction \ of liver fat content after bariatric surgery. Surg. Obes. Relat. 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F., Lee, S., Hahm, Y. T. & Sul, H. S. Expression and identification of \ p90 as the murine mitochondrial glycerol-3-\nphosphate acyltransferase. Biochemistry 32, 9486 9491 \(1993\).\r:172)/F 4/H/N/Rect[279.979 517.52 285.729 507.34]/Subtype/Link/Type/Annot>> endobj 136 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:62. Neschen, S. et al. Prevention of hepatic steatosis and hepatic insulin resistanc\ e in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice. Cell Metab. 2, 55 65 \(2005\).\r:173)/F 4/H/N/Rect[286.982 517.52 292.566 507.34]/Subtype/Link/Type/Annot>> endobj 137 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:20. Emdin, C. A. et al. A missense variant in mitochondrial amidoxime reducing com\ ponent 1 gene and protection against liver disease. 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Guan, M., Qu, L., Tan, W., Chen, L. & Wong, C. W. Hepatocyte nuclear factor-4 a\ lpha regulates liver triglyceride metabolism in part through secreted phospholipase A\(2\) GXIIB. Hepatology 53, 458 466 \(20\ 11\).\r:183)/F 4/H/N/Rect[118.035 162.77 122.667 152.59]/Subtype/Link/Type/Annot>> endobj 147 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:68. Liu, Q. et al. Activation of farnesoid X receptor promotes triglycerides lowerin\ g by suppressing phospholipase A2 G12B expression. Mol. Cell Endocrinol. 436, 93 101 \(2016\).\r:184)/F 4/H/N/Rect[123.858 162.77 129.502 152.59]/Subtype/Link/Type/Annot>> endobj 148 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:2. Blond, E. et al. EASL-EASD-EASO clinical practice guidelines for the management o\ f non-alcoholic fatty liver disease in severely obese people: do they lead to over-referral? 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Rev. 16, 3 34 \(1995\).\r:188)/F 4/H/N/Rect[443.601 689.52 448.338 679.34]/Subtype/Link/Type/Annot>> endobj 152 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:72. Wheatcroft, S. B. & Kearney, M. T. IGF-dependent and IGF-independent actions of \ IGF-binding protein-1 and -2: implications for metabolic homeostasis. Trends Endocrinol. Metab. 20, 153 162 \(2009\).\r:189)/F 4/H/N/Rect[449.658 689.52 454.935 679.34]/Subtype/Link/Type/Annot>> endobj 153 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:73. Adamek, A. & Kasprzak, A. Insulin-like growth factor \(IGF\) system in liver dise\ ases. Int. J. Mol. Sci. 19, 1308 \(2018\).\r:190)/F 4/H/N/Rect[434.85 668.02 440.077 657.84]/Subtype/Link/Type/Annot>> endobj 154 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:74. Guo, X. H. et al. Insulin-like growth factor binding protein-related protein 1 c\ ontributes to hepatic fibrogenesis. J. Dig. 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Detection of sharing by descent, long-\nrange phasing and haploty\ pe imputation. Nat. Genet. 40, 1068 1075 \(2008\).\r:199)/F 4/H/N/Rect[250.883 549.77 256.153 539.59]/Subtype/Link/Type/Annot>> endobj 191 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:82. Eggertsson, H. P. et al. Graphtyper enables population-scale genotyping using pa\ ngenome graphs. Nat. Genet. 49, \n1654 1660 \(2017\).\r:200)/F 4/H/N/Rect[217.754 506.77 223.287 496.59]/Subtype/Link/Type/Annot>> endobj 192 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:84. Jonsson, H. et al. Whole genome characterization of \nsequence diversity of 15,22\ 0 Icelanders. Sci. 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DBDS Genomic Cohort, a prospective and comprehensive resour\ ce for integrative and temporal analysis of genetic, environmental and lifestyle factors affecting health of blood donors. BMJ \ Open 9, e028401 \(2019\).\r:203)/F 4/H/N/Rect[75.5146 216.52 81.2813 206.34]/Subtype/Link/Type/Annot>> endobj 198 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:82. Eggertsson, H. P. et al. Graphtyper enables population-scale genotyping using p\ angenome graphs. Nat. Genet. 49, \n1654 1660 \(2017\).\r:204)/F 4/H/N/Rect[103.11 130.52 108.45 120.34]/Subtype/Link/Type/Annot>> endobj 199 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:85. Delaneau, O., Zagury, J. F., Robinson, M. R., Marchini, J. L. & Dermitzakis, E. \ T. Accurate, scalable and integrative haplotype estimation. Nat. Commun. 10, 5436 \(2019\).\r:205)/F 4/H/N/Rect[115.704 119.77 121.104 109.59]/Subtype/Link/Type/Annot>> endobj 200 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:83. Gudbjartsson, D. F. et al. Large-scale whole-genome \nsequencing of the Icelandic\ population. Nat. Genet. 47, \n435 444 \(2015\).\r:206)/F 4/H/N/Rect[151.67 76.7704 157.034 66.5899]/Subtype/Link/Type/Annot>> endobj 201 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:84. Jonsson, H. et al. Whole genome characterization of \nsequence diversity of 15,2\ 20 Icelanders. Sci. Data 4, \n170115 \(2017\).\r:207)/F 4/H/N/Rect[158.325 76.7704 164.047 66.5899]/Subtype/Link/Type/Annot>> endobj 202 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:79. Littlejohns, T. J. et al. The UK Biobank imaging enhancement of 100,000 partici\ pants: rationale, data collection, management and future directions. Nat. Commun. 11, 2624 \(2020\).\r:208)/F 4/H/N/Rect[464.721 657.27 470.136 647.09]/Subtype/Link/Type/Annot>> endobj 203 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:86. Reeder, S. B. et al. Iterative decomposition of water and fat with echo asymmetr\ y and least-squares estimation \(IDEAL\): application with fast spin-echo imaging. Magn. Reson. Med. 54, 636 644 \(2005\).\r:\ 209)/F 4/H/N/Rect[553.278 646.52 559.036 636.34]/Subtype/Link/Type/Annot>> endobj 204 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:87. Ma, J. Dixon techniques for water and fat imaging. J. Magn. Reson. Imaging 28\ , 543 558 \(2008\).\r:210)/F 4/H/N/Rect[442.588 485.27 448.023 475.09]/Subtype/Link/Type/Annot>> endobj 205 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:88. Yu, H. et al. Multiecho reconstruction for simultaneous water-fat decomposition \ and T2* estimation. J. Magn. Reson. 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XǹJE>-KydAaw(mCNx|~m 㤗%UɬWV뇫oPT@5+Ϛ0ygr~0OfK^љY=֤GAe0AL10R0 (wa8b@/IeOtt k0~ 8*nʲ|]|7\)pn꽱W#*v=ӗ_~5q65X*7  tVwp!Ȇ15&O7vqx]&Ջn//8@P/ ؅jL-};tMt!*6G#.w [k T kz\6ܴzmtjvFY~Ǘ[⬪4%-r endstream endobj 209 0 obj <>stream GPL Ghostscript 9.52 2022-10-13T14:22:53+05:30 2022-10-13T14:22:53+05:30 XeTeX output 2022.10.13:1419 uuid:ec69a37f-4d2f-11ed-0000-667d45fee4c3 application/pdf Untitled endstream endobj 210 0 obj <> endobj 211 0 obj <>stream GPL Ghostscript 9.52 2022-10-13T14:22:57+05:30 2022-10-13T14:22:57+05:30 XeTeX output 2022.10.13:1419 uuid:eecbfd7f-4d2f-11ed-0000-a3c7b8e2546e application/pdf Untitled endstream endobj 212 0 obj <> endobj 213 0 obj <>stream GPL Ghostscript 9.52 2022-10-13T14:22:58+05:30 2022-10-13T14:22:58+05:30 XeTeX output 2022.10.13:1420 uuid:ef6493ff-4d2f-11ed-0000-a3c7b8e2546e application/pdf Untitled endstream endobj 214 0 obj <> endobj 215 0 obj <>stream GPL Ghostscript 9.52 2022-10-13T14:22:59+05:30 2022-10-13T14:22:59+05:30 XeTeX output 2022.10.13:1420 uuid:effd2a7f-4d2f-11ed-0000-a0f1480e15bb application/pdf Untitled endstream endobj 216 0 obj <> endobj 217 0 obj <>stream GPL Ghostscript 9.52 2022-10-13T14:23+05:30 2022-10-13T14:23+05:30 XeTeX output 2022.10.13:1420 uuid:f095c0ff-4d2f-11ed-0000-a3c7b8e2546e application/pdf Untitled endstream endobj 218 0 obj <> endobj 219 0 obj <>stream GPL Ghostscript 9.52 2022-10-13T14:23:01+05:30 2022-10-13T14:23:01+05:30 XeTeX output 2022.10.13:1420 uuid:f12e577f-4d2f-11ed-0000-a3c7b8e2546e application/pdf Untitled endstream endobj 220 0 obj <> endobj 221 0 obj <>stream GPL Ghostscript 9.52 2022-10-13T14:22:54+05:30 2022-10-13T14:22:54+05:30 XeTeX output 2022.10.13:1421 uuid:ed0239ff-4d2f-11ed-0000-0ab3ab6f0149 application/pdf Untitled endstream endobj 222 0 obj <> endobj 223 0 obj <>stream GPL Ghostscript 9.52 2022-10-13T14:22:55+05:30 2022-10-13T14:22:55+05:30 XeTeX output 2022.10.13:1421 uuid:ed9ad07f-4d2f-11ed-0000-a65c4cb9b504 application/pdf Untitled endstream endobj 224 0 obj <> endobj 225 0 obj <> endobj 226 0 obj <> endobj 227 0 obj <> endobj 228 0 obj [229 0 R 230 0 R 231 0 R 232 0 R 233 0 R 234 0 R 235 0 R 236 0 R 237 0 R 238 0 R] endobj 229 0 obj <>/BS<>/Border[0 0 0]/F 4/H/N/Rect[39.685 30.6693 101.585 19.6693]/Subtype/Link/Type/Annot>> endobj 230 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:20. Emdin, C. A. et al. A missense variant in mitochondrial amidoxime reducing co\ mponent 1 gene and protection against liver disease. PLoS Genet. 16, e1008629 \(2020\).\r:213)/F 4/H/N/Rect[110.292 678.77 116.232 668.59]/Subtype/Link/Type/Annot>> endobj 231 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:28. Turley, P. et al. Multi-trait analysis of genome-wide association summary stati\ stics using MTAG. Nat. Genet. 50, 229 237 \(2018\).\r:214)/F 4/H/N/Rect[286.847 291.77 292.543 281.59]/Subtype/Link/Type/Annot>> endobj 232 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:90. Bulik-Sullivan, B. K. et al. LD score regression distinguishes confounding from \ polygenicity in genome-wide association studies. Nat. Genet. 47, 291 295 \(2015\).\r:215)/F 4/H/N/Rect[259.299 248.77 265.385 238.59]/Subtype/Link/Type/Annot>> endobj 233 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:91. Sveinbjornsson, G. et al. Weighting sequence variants based on their annotation \ increases power of whole-genome association studies. Nat. Genet. 48, 314 317 \(2016\).\r:216)/F 4/H/N/Rect[132.015 205.77 137.285 195.59]/Subtype/Link/Type/Annot>> endobj 234 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:92. Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29\ , 15 21 \(2013\).\r:217)/F 4/H/N/Rect[547.018 506.77 552.503 496.59]/Subtype/Link/Type/Annot>> endobj 235 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:93. Howe, K. L. et al. Ensembl 2021. Nucleic Acids Res. 49, \nD884 D891 \(2021\).\ \r:218)/F 4/H/N/Rect[553.642 506.77 559.054 496.59]/Subtype/Link/Type/Annot>> endobj 236 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:94. Bray, N. L., Pimentel, H., Melsted, P. & Pachter, L. Near-optimal probabilistic \ RNA-seq quantification. Nat. 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Snaebjarnarson Emil Sigurdsson Valgerdur Steinthorsdottir Michael Schwinn Gudmundur Thorgeirsson Gudmar Thorleifsson Ingileif Jonsdottir Henning Bundgaard Lincoln Nadauld Einar S. Bjornsson Ingrid C. Rulifson Thorunn Rafnar Gudmundur L. Norddahl Unnur Thorsteinsdottir Patrick Sulem Daniel F. 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USA 73, 1324 1328 \ \(1976\).\r:138)/F 4/H/N/Rect[448.993 431.52 454.581 421.34]/Subtype/Link/Type/Annot>> endobj 15 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 2 | Effects of sequence variants on PDFF compared with effects on liver dise\ ase, liver enzymes and lipids. \(a i\) Effects of sequence variants on PDFF \(n = 36,116\) compared with their effects o\ n ICD-10 code-diagnosed NAFL \(ncas:139)/F 4/H/N/Rect[324.938 399.303 329.463 389.09]/Subtype/Link/Type/Annot>> endobj 16 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:37. Bierut, L. J. et al. ADH1B is associated with alcohol \ndependence and alcohol co\ nsumption in populations \nof European and African ancestry. Mol. Psychiatry 17, \n445 450 \(2012\).\r:140)/F 4/H/N/Rect[338.039 367.053 343.312 356.84]/Subtype/Link/Type/Annot>> endobj 17 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:38. Feder, J. N. et al. A novel MHC class I-like gene is mutated in patients with he\ reditary haemochromatosis. Nat. Genet. 13, 399 408 \(1996\).\r:141)/F 4/H/N/Rect[452.529 367.053 458.124 356.84]/Subtype/Link/Type/Annot>> endobj 18 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 2 | Effects of sequence variants on PDFF compared with effects on liver dis\ ease, liver enzymes and lipids. \(a i\) Effects of sequence variants on PDFF \(n = 36,116\) compared with their effects \ on ICD-10 code-diagnosed NAFL \(nca:142)/F 4/H/N/Rect[432.147 345.52 436.619 335.34]/Subtype/Link/Type/Annot>> endobj 19 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:39. Thangapandi, V. R. et al. Loss of hepatic Mboat7 leads to liver fibrosis. Gut \ 70, 940 950 \(2021\).\r:143)/F 4/H/N/Rect[544.957 152.053 550.782 141.84]/Subtype/Link/Type/Annot>> endobj 20 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:41. Xia, M., Chandrasekaran, P., Rong, S., Fu, X. & Mitsche, M. A. Hepatic deletion \ of Mboat7 \(LPIAT1\) causes activation of SREBP-1c and fatty liver. J. Lipid Res. 62, 100031 \(2021\).\r:144)/F 4/H/N/Rect[553.773 152.053 558.988 141.84]/Subtype/Link/Type/Annot>> endobj 21 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:1. Younossi, Z. M. et al. Global epidemiology of nonalcoholic fatty liver disease-\ meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 64, 73 84 \(2016\).\r:102)/F 4/H/N/Rect[71.1774 743.27 73.2386 733.09]/Subtype/Link/Type/Annot>> endobj 22 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:8. Wong, R. J. et al. Nonalcoholic steatohepatitis is the second leading etiology of\ liver disease among adults awaiting liver transplantation in the United States. Gastroenterology 148, 547 555 \(2015\).\r:1\ 03)/F 4/H/N/Rect[74.5119 743.27 77.3349 733.09]/Subtype/Link/Type/Annot>> endobj 23 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:9. Younossi, Z. et al. Nonalcoholic steatohepatitis is the fastest growing cause of \ hepatocellular carcinoma in liver transplant candidates. Clin. Gastroenterol. Hepatol. 17, 748 755 e3 \(2019\).\r:104)/F 4/H/N/Rect[78.3614 743.27 80.9606 733.09]/Subtype/Link/Type/Annot>> endobj 24 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:10. Pazoki, R. et al. Genetic analysis in European ancestry individuals identifies 5\ 17 loci associated with liver enzymes. Nat. Commun. 12, 2579 \(2021\).\r:105)/F 4/H/N/Rect[73.6004 732.52 78.9694 722.34]/Subtype/Link/Type/Annot>> endobj 25 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:12. Chen, V. L. et al. Genome-wide association study of serum liver enzymes implicat\ es diverse metabolic and liver pathology. Nat. Commun. 12, 816 \(2021\).\r:106)/F 4/H/N/Rect[81.8514 732.52 86.6652 722.34]/Subtype/Link/Type/Annot>> endobj 26 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:13. Emdin, C. A. et al. Association of genetic variation with \ncirrhosis: a multi-tr\ ait genome-wide association and gene-environment interaction study. Gastroenterology 160, 1620 1633 e13 \(2021\).\r:107)/F 4/H/N/Rect[124.029 732.52 128.868 722.34]/Subtype/Link/Type/Annot>> endobj 27 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:14. Schwimmer, J. B. et al. Heritability of nonalcoholic fatty liver disease. Gastr\ oenterology 136, 1585 1592 \(2009\).\r:108)/F 4/H/N/Rect[173.022 732.52 178.026 722.34]/Subtype/Link/Type/Annot>> endobj 28 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:16. Jamialahmadi, O. et al. Exome-wide association study on alanine aminotransferase\ identifies sequence variants in the GPAM and APOE associated with fatty liver disease. Gastroenterology 160, 1634 1646 e7 \(\ 2021\).\r:109)/F 4/H/N/Rect[180.908 732.52 185.872 722.34]/Subtype/Link/Type/Annot>> endobj 29 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:17. Romeo, S. et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoho\ lic fatty liver disease. Nat. Genet. 40, 1461 1465 \(2008\).\r:110)/F 4/H/N/Rect[96.6375 721.803 101.272 711.59]/Subtype/Link/Type/Annot>> endobj 30 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:18. Kozlitina, J. et al. Exome-wide association study identifies a TM6SF2 variant th\ at confers susceptibility to nonalcoholic fatty liver disease. Nat. Genet. 46, 352 356 \(2014\).\r:111)/F 4/H/N/Rect[156.662 721.803 161.696 711.59]/Subtype/Link/Type/Annot>> endobj 31 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:19. Speliotes, E. K. et al. Genome-wide association analysis identifies variants ass\ ociated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 7, e1001324 \(2011\ \).\r:112)/F 4/H/N/Rect[208.745 721.803 213.644 711.59]/Subtype/Link/Type/Annot>> endobj 32 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:20. Emdin, C. A. et al. A missense variant in mitochondrial amidoxime reducing compo\ nent 1 gene and protection against liver disease. PLoS Genet. 16, e1008629 \(2020\).\r:113)/F 4/H/N/Rect[283.542 721.803 289.49 711.59]/Subtype/Link/Type/Annot>> endobj 33 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:21. Abul-Husn, N. S. et al. A protein-truncating HSD17B13 variant and protection fro\ m chronic liver disease. N. Engl. J. Med. 378, 1096 1106 \(2018\).\r:114)/F 4/H/N/Rect[224.756 700.27 229.508 690.09]/Subtype/Link/Type/Annot>> endobj 34 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:22. Browning, J. D. et al. Prevalence of hepatic steatosis in an urban population in\ the United States: impact of ethnicity. 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European Association for the Study of the Liver, European Association for the Study\ of Diabetes & European Association for the Study of Obesity. 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PL\ oS ONE 12, e0172921 \(2017\).\r:121)/F 4/H/N/Rect[255.474 377.77 261.098 367.59]/Subtype/Link/Type/Annot>> endobj 41 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:27. World Health Organization. ICD-10 : International Statistical Classification of Di\ seases and Related Health Problems, \ntenth revision, 2nd ed. \(World Health Organization, 2004\); \nhttps://apps.who.int/iris/\ handle/10665/42980\r:122)/F 4/H/N/Rect[206.231 324.053 210.945 313.84]/Subtype/Link/Type/Annot>> endobj 42 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:28. Turley, P. et al. Multi-trait analysis of genome-wide association summary statis\ tics using MTAG. Nat. Genet. 50, 229 237 \(2018\).\r:123)/F 4/H/N/Rect[202.953 259.52 208.502 249.34]/Subtype/Link/Type/Annot>> endobj 43 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Table 2 | GWASs with NAFL \(combination of PDFF and NAFL ICD-10 code diagnosis\)\ \r:124)/F 4/H/N/Rect[133.89 238.02 138.547 227.84]/Subtype/Link/Type/Annot>> endobj 44 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 2 | Effects of sequence variants on PDFF compared with effects on liver disea\ se, liver enzymes and lipids. \(a i\) Effects of sequence variants on PDFF \(n = 36,116\) compared with their effects on\ ICD-10 code-diagnosed NAFL \(ncase:125)/F 4/H/N/Rect[173.717 184.27 178.258 174.09]/Subtype/Link/Type/Annot>> endobj 45 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:17. Romeo, S. et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoh\ olic fatty liver disease. Nat. Genet. 40, 1461 1465 \(2008\).\r:126)/F 4/H/N/Rect[66.7051 119.77 70.8198 109.59]/Subtype/Link/Type/Annot>> endobj 46 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:29. Singal, A. G. et al. The effect of PNPLA3 on fibrosis progression and developmen\ t of hepatocellular carcinoma: a meta-analysis. Am. J. 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Commun. 10, 1499 \(2019\).\r:145)/F 4/H/N/Rect[113.811 173.52 119.171 163.34]/Subtype/Link/Type/Annot>> endobj 53 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:45. Shah, S. et al. Genome-wide association and Mendelian randomisation analysis pro\ vide insights into the pathogenesis of heart failure. Nat. Commun. 11, 163 \(2020\).\r:146)/F 4/H/N/Rect[121.998 173.52 127.168 163.34]/Subtype/Link/Type/Annot>> endobj 54 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 2 | Effects of sequence variants on PDFF compared with effects on liver di\ sease, liver enzymes and lipids. \(a i\) Effects of sequence variants on PDFF \(n = 36,116\) compared with their effects\ on ICD-10 code-diagnosed NAFL \(nc:147)/F 4/H/N/Rect[242.874 162.77 247.346 152.59]/Subtype/Link/Type/Annot>> endobj 55 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 3 | Pleiotropic effects of NAFLD variants. The effects of the identified \ variants with 51 phenotypes, including liver enzymes and lipid levels. The effect \(colored from red to blue\) on each phenotype \ is shown for the allele that increas:148)/F 4/H/N/Rect[264.404 162.77 268.916 152.59]/Subtype/Link/Type/Annot>> endobj 56 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 3 | Pleiotropic effects of NAFLD variants. The effects of the identified\ variants with 51 phenotypes, including liver enzymes and lipid levels. The effect \(colored from red to blue\) on each phenotype\ is shown for the allele that increa:149)/F 4/H/N/Rect[195.48 130.52 200.215 120.34]/Subtype/Link/Type/Annot>> endobj 57 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 3 | Pleiotropic effects of NAFLD variants. The effects of the identifie\ d variants with 51 phenotypes, including liver enzymes and lipid levels. The effect \(colored from red to blue\) on each phenotyp\ e is shown for the allele that incre:150)/F 4/H/N/Rect[232.023 109.02 236.468 98.8399]/Subtype/Link/Type/Annot>> endobj 58 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 4 | Association pattern of missense and loss-of-function variants in GPAM a\ nd MTARC1. \(a,b\) Plots show a similar association pattern of common missense variants in MTARC1 \(a\) and GPAM \(\ b\) with selected phenotypes. On the:151)/F 4/H/N/Rect[252.653 109.02 257.368 98.8399]/Subtype/Link/Type/Annot>> endobj 59 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:46. Havemeyer, A. et al. Identification of the missing component \nin the mitochondri\ al benzamidoxime prodrug-converting \nsystem as a novel molybdenum enzyme. J. Biol. Chem. 281, 34796 34802 \(2006\).\r:152)/F 4/H/N/Rect[464.781 130.52 470.523 120.34]/Subtype/Link/Type/Annot>> endobj 60 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:48. Yet, S. F., Lee, S., Hahm, Y. T. & Sul, H. S. Expression and identification of p\ 90 as the murine mitochondrial glycerol-3-\nphosphate acyltransferase. Biochemistry 32, 9486 9491 \(1993\).\r:153)/F 4/H/N/Rect[473.329 130.52 478.984 120.34]/Subtype/Link/Type/Annot>> endobj 61 0 obj <>/BS<>/Border[0 0 0]/Dest(SpringerNature_NatGenet_1199.indd:Fig. 4 | Association pattern of missense and loss-of-function variants in GPAM \ and MTARC1. \(a,b\) Plots show a similar association pattern of common missense variants in MTARC1 \(a\) and GPAM \ \(b\) with selected phenotypes. 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