| Title | A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation |
| Author | Vujkovic，Marijana1,2; Ramdas，Shweta3; Lorenz，Kim M.1,3,4; Guo，Xiuqing5; Darlay，Rebecca6; Cordell，Heather J.6; He，Jing7; Gindin，Yevgeniy8; Chung，Chuhan8; Myers，Robert P.8,9; Schneider，Carolin V.3; Park，Joseph2,3; Lee，Kyung Min10; Serper，Marina1,2; Carr，Rotonya M.11; Kaplan，David E.1,2; Haas，Mary E.12; MacLean，Matthew T.3; Witschey，Walter R.13; Zhu，Xiang14,15,16,17; Tcheandjieu，Catherine14,18; Kember，Rachel L.19,20; Kranzler，Henry R.19,20; Verma，Anurag1,3; Giri，Ayush21; Klarin，Derek M.14,22,23; Sun，Yan V.24,25; Huang，Jie26  ; Huffman，Jennifer E.27; Townsend Creasy，Kate3; Hand，Nicholas J.3; Liu，Ching Ti28; Long，Michelle T.29; Yao，Jie5; Budoff，Matthew30; Tan，Jingyi5; Li，Xiaohui5; Lin，Henry J.5; Chen，Yii Der Ida5; Taylor，Kent D.5; Chang，Ruey Kang5; Krauss，Ronald M.31; Vilarinho，Silvia32; Brancale，Joseph32; Nielsen，Jonas B.33; Locke，Adam E.33; Jones，Marcus B.33; Verweij，Niek33; Baras，Aris33; Reddy，K. Rajender2; Neuschwander-Tetri，Brent A.34; Schwimmer，Jeffrey B.35; Sanyal，Arun J.36; Chalasani，Naga37; Ryan，Kathleen A.38; Mitchell，Braxton D.38; Gill，Dipender39; Wells，Andrew D.40,41; Manduchi，Elisabetta3; Saiman，Yedidya42; Mahmud，Nadim43; Miller，Donald R.44,45; Reaven，Peter D.46,47; Phillips，Lawrence S.24,48; Muralidhar，Sumitra49; DuVall，Scott L.10,50; Lee，Jennifer S.14,18; Assimes，Themistocles L.14,18,51; Pyarajan，Saiju27,52,53; Cho，Kelly27,52,53; Edwards，Todd L.54,55; Damrauer，Scott M.1,3,56; Wilson，Peter W.24,57; Gaziano，J. Michael27,52; O’Donnell，Christopher J.27,52,53; Khera，Amit V.23,53,58; Grant，Struan F.A.3,59,60; Brown，Christopher D.3; Tsao，Philip S.14,18,51; Saleheen，Danish61,62,63; Lotta，Luca A.33; Bastarache，Lisa7; Anstee，Quentin M.64,65; Daly，Ann K.65; Meigs，James B.23,53,66; Rotter，Jerome I.5; Lynch，Julie A.10,50,67; Rader，Daniel J.2,3; Voight，Benjamin F.1,3,4,68 ; Chang，Kyong Mi1,2
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| Corresponding Author | Voight，Benjamin F. |
| Publication Years | 2022
|
| DOI | |
| Source Title | |
| ISSN | 1061-4036
|
| EISSN | 1546-1718
|
| Abstract | Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P < 5 × 10). External replication in histology-defined NAFLD cohorts (7,397 cases and 56,785 controls) or radiologic imaging cohorts (n = 44,289) replicated 17 single-nucleotide polymorphisms (SNPs) (P < 6.5 × 10), of which 9 were new (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH and IFI30). Pleiotropy analysis showed that 61 of 77 multiancestry and all 17 replicated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD. |
| URL | [Source Record] |
| Indexed By | |
| Language | English
|
| Important Publications | NI Journal Papers
|
| SUSTech Authorship | Others
|
| WOS Accession No | WOS:000805090300004
|
| ESI Research Field | MOLECULAR BIOLOGY & GENETICS
|
| Scopus EID | 2-s2.0-85132074767
|
| Data Source | Scopus
|
| Citation statistics |
Cited Times [WOS]:20
|
| Document Type | Journal Article |
| Identifier | http://kc.sustech.edu.cn/handle/2SGJ60CL/355717 |
| Department | School of Public Health and Emergency Management |
| Affiliation | 1.Corporal Michael J. Crescenz VA Medical Center,Philadelphia,United States 2.Department of Medicine,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States 3.Department of Genetics,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States 4.Department of Systems Pharmacology and Translational Therapeutics,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States 5.The Institute for Translational Genomics and Population Sciences,Department of Pediatrics,The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center,Torrance,United States 6.Population Health Sciences Institute,Newcastle University,Newcastle upon Tyne,United Kingdom 7.Department of Biomedical Informatics,Vanderbilt University Medical Center,Nashville,United States 8.Gilead Sciences,Inc.,Foster City,United States 9.The Liver Company,Palo Alto,United States 10.VA Salt Lake City Health Care System,Salt Lake City,United States 11.Division of Gastroenterology,University of Washington,Seattle,United States 12.Broad Institute of MIT and Harvard,Cambridge,United States 13.Department of Radiology,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States 14.VA Palo Alto Health Care System,Palo Alto,United States 15.Department of Statistics,The Pennsylvania State University,University Park,United States 16.Huck Institutes of the Life Sciences,The Pennsylvania State University,University Park,United States 17.Department of Statistics,Stanford University,Stanford,United States 18.Department of Medicine,Stanford University School of Medicine,Stanford,United States 19.Mental Illness Research Education and Clinical Center,Corporal Michael J. Crescenz VA Medical Center,Philadelphia,United States 20.Department of Psychiatry,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States 21.Department of Obstetrics and Gynecology,Vanderbilt University Medical Center,Nashville,United States 22.Division of Vascular Surgery,Stanford University School of Medicine,Palo Alto,United States 23.Program in Medical and Population Genetics,Broad Institute of MIT and Harvard,Cambridge,United States 24.Atlanta VA Medical Center,Decatur,United States 25.Department of Epidemiology,Emory University Rollins School of Public Health,Atlanta,United States 26.School of Public Health and Emergency Management,Southern University of Science and Technology,Shenzhen,Guangdong,China 27.VA Boston Healthcare System,Boston,United States 28.Department of Biostatistics,Boston University School of Public Health,Boston,United States 29.Department of Medicine,Section of Gastroenterology,Boston University School of Medicine,Boston,United States 30.Department of Cardiology,The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center,Torrance,United States 31.Departments of Pediatrics and Medicine,University of California,San Francisco,San Francisco,United States 32.Section of Digestive Diseases,Department of Internal Medicine,and Department of Pathology,Yale School of Medicine,New Haven,United States 33.Regeneron Genetics Center,Tarrytown,United States 34.Department of Internal Medicine,Saint Louis University,St. Louis,United States 35.Department of Pediatrics,University of California San Diego,La Jolla,United States 36.Department of Internal Medicine,Virginia Commonwealth University School of Medicine,Richmond,United States 37.Department of Medicine,Indiana University School of Medicine,Indianapolis,United States 38.Program for Personalized and Genomic Medicine,Division of Endocrinology,Diabetes and Nutrition,Department of Medicine,University of Maryland School of Medicine,Baltimore,United States 39.Department of Epidemiology and Biostatistics,School of Public Health,Imperial College London,London,United Kingdom 40.Department of Pathology and Laboratory Medicine,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States 41.Department of Pathology,Children’s Hospital of Philadelphia,Philadelphia,United States 42.Department of Medicine,Section of Hepatology,Lewis Katz School of Medicine at Temple University,Temple University Hospital,Philadelphia,United States 43.Department of Medicine,Division of Gastroenterology,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States 44.Center for Healthcare Organization and Implementation Research,Bedford VA Healthcare System,Bedford,United States 45.Center for Population Health,Department of Biomedical and Nutritional Sciences,University of Massachusetts,Lowell,United States 46.Phoenix VA Health Care System,Phoenix,United States 47.College of Medicine,University of Arizona,Phoenix,United States 48.Division of Endocrinology,Emory University School of Medicine,Atlanta,United States 49.Office of Research and Development,Veterans Health Administration,Washington,United States 50.Department of Medicine,University of Utah School of Medicine,Salt Lake City,United States 51.Stanford Cardiovascular Institute,Stanford University School of Medicine,Stanford,United States 52.Department of Medicine,Brigham Women’s Hospital,Boston,United States 53.Department of Medicine,Harvard Medical School,Boston,United States 54.Nashville VA Medical Center,Nashville,United States 55.Division of Epidemiology,Department of Medicine,Vanderbilt Genetics Institute,Vanderbilt University Medical Center,Nashville,United States 56.Department of Surgery,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States 57.Division of Cardiology,Emory University School of Medicine,Atlanta,United States 58.Center for Genomic Medicine,Massachusetts General Hospital,Boston,United States 59.Department of Pediatrics,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States 60.Division of Human Genetics,Children’s Hospital of Philadelphia,Philadelphia,United States 61.Department of Medicine,Columbia University Irving Medical Center,New York,United States 62.Department of Cardiology,Columbia University Irving Medical Center,New York,United States 63.Center for Non-Communicable Diseases,Karachi,Sindh,Pakistan 64.Faculty of Medical Sciences,Newcastle University,Newcastle upon Tyne,United Kingdom 65.Newcastle NIHR Biomedical Research Centre,Newcastle upon Tyne Hospitals NHS Foundation Trust,Newcastle upon Tyne,United Kingdom 66.Division of General Internal Medicine,Massachusetts General Hospital,Boston,United States 67.College of Nursing and Health Sciences,University of Massachusetts,Lowell,United States 68.Institute of Translational Medicine and Therapeutics,University of Pennsylvania Perelman School of Medicine,Philadelphia,United States |
| Recommended Citation GB/T 7714 |
Vujkovic，Marijana,Ramdas，Shweta,Lorenz，Kim M.,et al. A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation[J]. NATURE GENETICS,2022.
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| APA |
Vujkovic，Marijana.,Ramdas，Shweta.,Lorenz，Kim M..,Guo，Xiuqing.,Darlay，Rebecca.,...&Chang，Kyong Mi.(2022).A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation.NATURE GENETICS.
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| MLA |
Vujkovic，Marijana,et al."A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation".NATURE GENETICS (2022).
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| s41588-022-01078-z.p（8142KB） | Open Access | -- | View | |||
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