Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program
Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Vete...
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| Veröffentlicht in: | PloS one 2020-08, Vol.15 (8), p.e0237430-e0237430 |
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| creator | Serper, Marina Vujkovic, Marijana Kaplan, David E Carr, Rotonya M Lee, Kyung Min Shao, Qing Miller, Donald R Reaven, Peter D Phillips, Lawrence S O'Donnell, Christopher J Meigs, James B Wilson, Peter W F Vickers-Smith, Rachel Kranzler, Henry R Justice, Amy C Gaziano, John M Muralidhar, Sumitra Pyarajan, Saiju DuVall, Scott L Assimes, Themistocles L Lee, Jennifer S Tsao, Philip S Rader, Daniel J Damrauer, Scott M Lynch, Julie A Saleheen, Danish Voight, Benjamin F Chang, Kyong-Mi |
| description | Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans.
MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts.
Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P |
| doi_str_mv | 10.1371/journal.pone.0237430 |
| format | Article |
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MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts.
Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis.
We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0237430</identifier><identifier>PMID: 32841307</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>17-Hydroxysteroid Dehydrogenases - genetics ; Abdomen - diagnostic imaging ; Adaptor Proteins, Signal Transducing - genetics ; Aged ; Alanine ; Alanine Transaminase - genetics ; Alanine Transaminase - metabolism ; Alcohol use ; Attenuation ; Authorship ; Biology and Life Sciences ; Biopsy ; Computer and Information Sciences ; Diagnosis ; Disease control ; Electronic Health Records ; Electronic medical records ; Endocrinology ; Epidemiology ; Fatty liver ; Female ; Fibrosis ; Gene polymorphism ; Genetic aspects ; Genetic diversity ; Genetic Loci ; Genetic Predisposition to Disease ; Genetic variance ; Genetic Variation ; Genetics ; Health aspects ; Health care policy ; Health risks ; Hospitals ; Humans ; Identification and classification ; Informatics ; Infrastructure ; Lipase - genetics ; Liver ; Liver - pathology ; Liver diseases ; Loci ; Lysophospholipase - genetics ; Male ; Medical imaging ; Medicine ; Medicine and Health Sciences ; Membrane Proteins - genetics ; Metabolism ; Middle Aged ; Non-alcoholic Fatty Liver Disease - ethnology ; Non-alcoholic Fatty Liver Disease - genetics ; Non-alcoholic Fatty Liver Disease - pathology ; Phenotype ; Phenotypes ; Physical Sciences ; Population studies ; Public health ; R&D ; Research & development ; Risk analysis ; Risk Factors ; Rogers, Edith Nourse ; Sensitivity analysis ; Veterans ; Veterans health care ; Womens health</subject><ispartof>PloS one, 2020-08, Vol.15 (8), p.e0237430-e0237430</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c622t-c56fb262a2202b3c9424632b5f637d6558c47f633319faf6d62681ced8e753013</citedby><cites>FETCH-LOGICAL-c622t-c56fb262a2202b3c9424632b5f637d6558c47f633319faf6d62681ced8e753013</cites><orcidid>0000-0002-3839-336X ; 0000-0003-4899-2160 ; 0000-0003-4924-5714 ; 0000-0002-6205-9994 ; 0000-0003-2349-0009 ; 0000-0002-2439-2657 ; 0000-0002-7224-8916</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447043/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447043/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32841307$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Palmer, Nicholette D.</contributor><creatorcontrib>Serper, Marina</creatorcontrib><creatorcontrib>Vujkovic, Marijana</creatorcontrib><creatorcontrib>Kaplan, David E</creatorcontrib><creatorcontrib>Carr, Rotonya M</creatorcontrib><creatorcontrib>Lee, Kyung Min</creatorcontrib><creatorcontrib>Shao, Qing</creatorcontrib><creatorcontrib>Miller, Donald R</creatorcontrib><creatorcontrib>Reaven, Peter D</creatorcontrib><creatorcontrib>Phillips, Lawrence S</creatorcontrib><creatorcontrib>O'Donnell, Christopher J</creatorcontrib><creatorcontrib>Meigs, James B</creatorcontrib><creatorcontrib>Wilson, Peter W F</creatorcontrib><creatorcontrib>Vickers-Smith, Rachel</creatorcontrib><creatorcontrib>Kranzler, Henry R</creatorcontrib><creatorcontrib>Justice, Amy C</creatorcontrib><creatorcontrib>Gaziano, John M</creatorcontrib><creatorcontrib>Muralidhar, Sumitra</creatorcontrib><creatorcontrib>Pyarajan, Saiju</creatorcontrib><creatorcontrib>DuVall, Scott L</creatorcontrib><creatorcontrib>Assimes, Themistocles L</creatorcontrib><creatorcontrib>Lee, Jennifer S</creatorcontrib><creatorcontrib>Tsao, Philip S</creatorcontrib><creatorcontrib>Rader, Daniel J</creatorcontrib><creatorcontrib>Damrauer, Scott M</creatorcontrib><creatorcontrib>Lynch, Julie A</creatorcontrib><creatorcontrib>Saleheen, Danish</creatorcontrib><creatorcontrib>Voight, Benjamin F</creatorcontrib><creatorcontrib>Chang, Kyong-Mi</creatorcontrib><creatorcontrib>VA Million Veteran Program</creatorcontrib><creatorcontrib>on behalf of the VA Million Veteran Program</creatorcontrib><title>Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans.
MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts.
Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis.
We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.</description><subject>17-Hydroxysteroid Dehydrogenases - genetics</subject><subject>Abdomen - diagnostic imaging</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Aged</subject><subject>Alanine</subject><subject>Alanine Transaminase - genetics</subject><subject>Alanine Transaminase - metabolism</subject><subject>Alcohol use</subject><subject>Attenuation</subject><subject>Authorship</subject><subject>Biology and Life Sciences</subject><subject>Biopsy</subject><subject>Computer and Information Sciences</subject><subject>Diagnosis</subject><subject>Disease control</subject><subject>Electronic Health Records</subject><subject>Electronic medical records</subject><subject>Endocrinology</subject><subject>Epidemiology</subject><subject>Fatty liver</subject><subject>Female</subject><subject>Fibrosis</subject><subject>Gene polymorphism</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Loci</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic variance</subject><subject>Genetic Variation</subject><subject>Genetics</subject><subject>Health aspects</subject><subject>Health care policy</subject><subject>Health risks</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Informatics</subject><subject>Infrastructure</subject><subject>Lipase - genetics</subject><subject>Liver</subject><subject>Liver - pathology</subject><subject>Liver diseases</subject><subject>Loci</subject><subject>Lysophospholipase - genetics</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Medicine</subject><subject>Medicine and Health Sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Non-alcoholic Fatty Liver Disease - ethnology</subject><subject>Non-alcoholic Fatty Liver Disease - genetics</subject><subject>Non-alcoholic Fatty Liver Disease - pathology</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Physical Sciences</subject><subject>Population studies</subject><subject>Public health</subject><subject>R&D</subject><subject>Research & development</subject><subject>Risk analysis</subject><subject>Risk Factors</subject><subject>Rogers, Edith Nourse</subject><subject>Sensitivity analysis</subject><subject>Veterans</subject><subject>Veterans health care</subject><subject>Womens 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a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program</title><author>Serper, Marina ; Vujkovic, Marijana ; Kaplan, David E ; Carr, Rotonya M ; Lee, Kyung Min ; Shao, Qing ; Miller, Donald R ; Reaven, Peter D ; Phillips, Lawrence S ; O'Donnell, Christopher J ; Meigs, James B ; Wilson, Peter W F ; Vickers-Smith, Rachel ; Kranzler, Henry R ; Justice, Amy C ; Gaziano, John M ; Muralidhar, Sumitra ; Pyarajan, Saiju ; DuVall, Scott L ; Assimes, Themistocles L ; Lee, Jennifer S ; Tsao, Philip S ; Rader, Daniel J ; Damrauer, Scott M ; Lynch, Julie A ; Saleheen, Danish ; Voight, Benjamin F ; Chang, Kyong-Mi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c622t-c56fb262a2202b3c9424632b5f637d6558c47f633319faf6d62681ced8e753013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>17-Hydroxysteroid Dehydrogenases - genetics</topic><topic>Abdomen - diagnostic imaging</topic><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Aged</topic><topic>Alanine</topic><topic>Alanine Transaminase - genetics</topic><topic>Alanine Transaminase - metabolism</topic><topic>Alcohol use</topic><topic>Attenuation</topic><topic>Authorship</topic><topic>Biology and Life Sciences</topic><topic>Biopsy</topic><topic>Computer and Information Sciences</topic><topic>Diagnosis</topic><topic>Disease control</topic><topic>Electronic Health Records</topic><topic>Electronic medical records</topic><topic>Endocrinology</topic><topic>Epidemiology</topic><topic>Fatty liver</topic><topic>Female</topic><topic>Fibrosis</topic><topic>Gene polymorphism</topic><topic>Genetic aspects</topic><topic>Genetic diversity</topic><topic>Genetic Loci</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetic variance</topic><topic>Genetic Variation</topic><topic>Genetics</topic><topic>Health aspects</topic><topic>Health care policy</topic><topic>Health risks</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Identification and classification</topic><topic>Informatics</topic><topic>Infrastructure</topic><topic>Lipase - genetics</topic><topic>Liver</topic><topic>Liver - pathology</topic><topic>Liver diseases</topic><topic>Loci</topic><topic>Lysophospholipase - genetics</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Medicine</topic><topic>Medicine and Health Sciences</topic><topic>Membrane Proteins - genetics</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Non-alcoholic Fatty Liver Disease - ethnology</topic><topic>Non-alcoholic Fatty Liver Disease - genetics</topic><topic>Non-alcoholic Fatty Liver Disease - pathology</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Physical Sciences</topic><topic>Population studies</topic><topic>Public health</topic><topic>R&D</topic><topic>Research & development</topic><topic>Risk analysis</topic><topic>Risk Factors</topic><topic>Rogers, Edith Nourse</topic><topic>Sensitivity analysis</topic><topic>Veterans</topic><topic>Veterans health care</topic><topic>Womens health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Serper, Marina</creatorcontrib><creatorcontrib>Vujkovic, Marijana</creatorcontrib><creatorcontrib>Kaplan, David E</creatorcontrib><creatorcontrib>Carr, Rotonya M</creatorcontrib><creatorcontrib>Lee, Kyung Min</creatorcontrib><creatorcontrib>Shao, Qing</creatorcontrib><creatorcontrib>Miller, Donald R</creatorcontrib><creatorcontrib>Reaven, Peter D</creatorcontrib><creatorcontrib>Phillips, Lawrence S</creatorcontrib><creatorcontrib>O'Donnell, Christopher J</creatorcontrib><creatorcontrib>Meigs, James B</creatorcontrib><creatorcontrib>Wilson, Peter W F</creatorcontrib><creatorcontrib>Vickers-Smith, Rachel</creatorcontrib><creatorcontrib>Kranzler, Henry R</creatorcontrib><creatorcontrib>Justice, Amy C</creatorcontrib><creatorcontrib>Gaziano, John M</creatorcontrib><creatorcontrib>Muralidhar, Sumitra</creatorcontrib><creatorcontrib>Pyarajan, Saiju</creatorcontrib><creatorcontrib>DuVall, Scott L</creatorcontrib><creatorcontrib>Assimes, Themistocles L</creatorcontrib><creatorcontrib>Lee, Jennifer S</creatorcontrib><creatorcontrib>Tsao, Philip S</creatorcontrib><creatorcontrib>Rader, Daniel J</creatorcontrib><creatorcontrib>Damrauer, Scott M</creatorcontrib><creatorcontrib>Lynch, Julie A</creatorcontrib><creatorcontrib>Saleheen, Danish</creatorcontrib><creatorcontrib>Voight, Benjamin F</creatorcontrib><creatorcontrib>Chang, Kyong-Mi</creatorcontrib><creatorcontrib>VA Million Veteran Program</creatorcontrib><creatorcontrib>on behalf of the VA Million Veteran Program</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In 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Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Serper, Marina</au><au>Vujkovic, Marijana</au><au>Kaplan, David E</au><au>Carr, Rotonya M</au><au>Lee, Kyung Min</au><au>Shao, Qing</au><au>Miller, Donald R</au><au>Reaven, Peter D</au><au>Phillips, Lawrence S</au><au>O'Donnell, Christopher J</au><au>Meigs, James B</au><au>Wilson, Peter W F</au><au>Vickers-Smith, Rachel</au><au>Kranzler, Henry R</au><au>Justice, Amy C</au><au>Gaziano, John M</au><au>Muralidhar, Sumitra</au><au>Pyarajan, Saiju</au><au>DuVall, Scott L</au><au>Assimes, Themistocles L</au><au>Lee, Jennifer S</au><au>Tsao, Philip S</au><au>Rader, Daniel J</au><au>Damrauer, Scott M</au><au>Lynch, Julie A</au><au>Saleheen, Danish</au><au>Voight, Benjamin F</au><au>Chang, Kyong-Mi</au><au>Palmer, Nicholette D.</au><aucorp>VA Million Veteran Program</aucorp><aucorp>on behalf of the VA Million Veteran Program</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2020-08-25</date><risdate>2020</risdate><volume>15</volume><issue>8</issue><spage>e0237430</spage><epage>e0237430</epage><pages>e0237430-e0237430</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans.
MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts.
Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis.
We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>32841307</pmid><doi>10.1371/journal.pone.0237430</doi><tpages>e0237430</tpages><orcidid>https://orcid.org/0000-0002-3839-336X</orcidid><orcidid>https://orcid.org/0000-0003-4899-2160</orcidid><orcidid>https://orcid.org/0000-0003-4924-5714</orcidid><orcidid>https://orcid.org/0000-0002-6205-9994</orcidid><orcidid>https://orcid.org/0000-0003-2349-0009</orcidid><orcidid>https://orcid.org/0000-0002-2439-2657</orcidid><orcidid>https://orcid.org/0000-0002-7224-8916</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2020-08, Vol.15 (8), p.e0237430-e0237430 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2437106817 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 17-Hydroxysteroid Dehydrogenases - genetics Abdomen - diagnostic imaging Adaptor Proteins, Signal Transducing - genetics Aged Alanine Alanine Transaminase - genetics Alanine Transaminase - metabolism Alcohol use Attenuation Authorship Biology and Life Sciences Biopsy Computer and Information Sciences Diagnosis Disease control Electronic Health Records Electronic medical records Endocrinology Epidemiology Fatty liver Female Fibrosis Gene polymorphism Genetic aspects Genetic diversity Genetic Loci Genetic Predisposition to Disease Genetic variance Genetic Variation Genetics Health aspects Health care policy Health risks Hospitals Humans Identification and classification Informatics Infrastructure Lipase - genetics Liver Liver - pathology Liver diseases Loci Lysophospholipase - genetics Male Medical imaging Medicine Medicine and Health Sciences Membrane Proteins - genetics Metabolism Middle Aged Non-alcoholic Fatty Liver Disease - ethnology Non-alcoholic Fatty Liver Disease - genetics Non-alcoholic Fatty Liver Disease - pathology Phenotype Phenotypes Physical Sciences Population studies Public health R&D Research & development Risk analysis Risk Factors Rogers, Edith Nourse Sensitivity analysis Veterans Veterans health care Womens health |
| title | Validating a non-invasive, ALT-based non-alcoholic fatty liver phenotype in the million veteran program |
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