The Health Impact of MAFLD, a Novel Disease Cluster of NAFLD, Is Amplified by the Integrated Effect of Fatty Liver Disease–Related Genetic Variants
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed disease category that derived from non-alcoholic fatty liver disease. The impact of MAFLD on health events has not been investigated. UK Biobank participants were diagnosed for whether MAFLD presented at baseline. Five...
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| Veröffentlicht in: | Clinical gastroenterology and hepatology 2022-04, Vol.20 (4), p.e855-e875 |
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| creator | Liu, Zhenqiu Suo, Chen Shi, Oumin Lin, Chunqing Zhao, Renjia Yuan, Huangbo Jin, Li Zhang, Tiejun Chen, Xingdong |
| description | Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed disease category that derived from non-alcoholic fatty liver disease. The impact of MAFLD on health events has not been investigated.
UK Biobank participants were diagnosed for whether MAFLD presented at baseline. Five genetic variants (PNPLA3 rs738409 C/G, TM6SF2 rs58542926 C/T, GCKR rs1260326 T/C, MBOAT7 rs641738 C/T, and HSD17B13 rs72613567 T/TA) were integrated into a genetic risk score (GRS). Cox proportional hazard model was used to examine the association of MAFLD with incident diseases.
A total of 160 979 (38.0%, 95% confidence interval [CI] 37.9%, 38.2%) participants out of 423 252 were diagnosed as MAFLD. Compared with participants without MAFLD, MAFLD cases had multivariate adjusted hazard ratio (HR) for liver cancer of 1.59 (95% CI, 1.28, 1.98), cirrhosis of 2.77 (2.29, 3.36), other liver diseases of 2.09 (1.95, 2.24), cardiovascular diseases of 1.39 (1.34, 1.44), renal diseases of 1.56 (1.48, 1.65), and cancers of 1.07 (1.05, 1.10). The impact of MAFLD, especially on hepatic events, was amplified by high GRS, of which the genetic variations in PNPLA3, TM6SF2, and MBOAT7 play the principal roles. MAFLD case with normal body weight is also associated with an increased risk of hepatic outcomes, but the genetic factor seems do not influence the risk in this subpopulation.
MAFLD is independently associated with an increased risk of both intrahepatic and extrahepatic events. Fatty liver disease related genetic variants amplify the effect of MAFLD on disease outcomes.
[Display omitted] |
| doi_str_mv | 10.1016/j.cgh.2020.12.033 |
| format | Article |
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UK Biobank participants were diagnosed for whether MAFLD presented at baseline. Five genetic variants (PNPLA3 rs738409 C/G, TM6SF2 rs58542926 C/T, GCKR rs1260326 T/C, MBOAT7 rs641738 C/T, and HSD17B13 rs72613567 T/TA) were integrated into a genetic risk score (GRS). Cox proportional hazard model was used to examine the association of MAFLD with incident diseases.
A total of 160 979 (38.0%, 95% confidence interval [CI] 37.9%, 38.2%) participants out of 423 252 were diagnosed as MAFLD. Compared with participants without MAFLD, MAFLD cases had multivariate adjusted hazard ratio (HR) for liver cancer of 1.59 (95% CI, 1.28, 1.98), cirrhosis of 2.77 (2.29, 3.36), other liver diseases of 2.09 (1.95, 2.24), cardiovascular diseases of 1.39 (1.34, 1.44), renal diseases of 1.56 (1.48, 1.65), and cancers of 1.07 (1.05, 1.10). The impact of MAFLD, especially on hepatic events, was amplified by high GRS, of which the genetic variations in PNPLA3, TM6SF2, and MBOAT7 play the principal roles. MAFLD case with normal body weight is also associated with an increased risk of hepatic outcomes, but the genetic factor seems do not influence the risk in this subpopulation.
MAFLD is independently associated with an increased risk of both intrahepatic and extrahepatic events. Fatty liver disease related genetic variants amplify the effect of MAFLD on disease outcomes.
[Display omitted]</description><identifier>ISSN: 1542-3565</identifier><identifier>EISSN: 1542-7714</identifier><identifier>DOI: 10.1016/j.cgh.2020.12.033</identifier><identifier>PMID: 33387670</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Cardiovascular Disease ; Cirrhosis ; Disease Hotspot ; Genetic Variants ; Humans ; Lipase - genetics ; Liver Cancer ; MAFLD ; Membrane Proteins - genetics ; NAFLD ; Non-alcoholic Fatty Liver Disease - epidemiology ; Non-alcoholic Fatty Liver Disease - genetics ; Polymorphism, Single Nucleotide</subject><ispartof>Clinical gastroenterology and hepatology, 2022-04, Vol.20 (4), p.e855-e875</ispartof><rights>2022 AGA Institute</rights><rights>Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-1ec09fc3266a78c11574dab9ea70dadf6728a3823db255f5045a41eb15c70e223</citedby><cites>FETCH-LOGICAL-c353t-1ec09fc3266a78c11574dab9ea70dadf6728a3823db255f5045a41eb15c70e223</cites><orcidid>0000-0003-3763-160X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cgh.2020.12.033$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33387670$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Zhenqiu</creatorcontrib><creatorcontrib>Suo, Chen</creatorcontrib><creatorcontrib>Shi, Oumin</creatorcontrib><creatorcontrib>Lin, Chunqing</creatorcontrib><creatorcontrib>Zhao, Renjia</creatorcontrib><creatorcontrib>Yuan, Huangbo</creatorcontrib><creatorcontrib>Jin, Li</creatorcontrib><creatorcontrib>Zhang, Tiejun</creatorcontrib><creatorcontrib>Chen, Xingdong</creatorcontrib><title>The Health Impact of MAFLD, a Novel Disease Cluster of NAFLD, Is Amplified by the Integrated Effect of Fatty Liver Disease–Related Genetic Variants</title><title>Clinical gastroenterology and hepatology</title><addtitle>Clin Gastroenterol Hepatol</addtitle><description>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed disease category that derived from non-alcoholic fatty liver disease. The impact of MAFLD on health events has not been investigated.
UK Biobank participants were diagnosed for whether MAFLD presented at baseline. Five genetic variants (PNPLA3 rs738409 C/G, TM6SF2 rs58542926 C/T, GCKR rs1260326 T/C, MBOAT7 rs641738 C/T, and HSD17B13 rs72613567 T/TA) were integrated into a genetic risk score (GRS). Cox proportional hazard model was used to examine the association of MAFLD with incident diseases.
A total of 160 979 (38.0%, 95% confidence interval [CI] 37.9%, 38.2%) participants out of 423 252 were diagnosed as MAFLD. Compared with participants without MAFLD, MAFLD cases had multivariate adjusted hazard ratio (HR) for liver cancer of 1.59 (95% CI, 1.28, 1.98), cirrhosis of 2.77 (2.29, 3.36), other liver diseases of 2.09 (1.95, 2.24), cardiovascular diseases of 1.39 (1.34, 1.44), renal diseases of 1.56 (1.48, 1.65), and cancers of 1.07 (1.05, 1.10). The impact of MAFLD, especially on hepatic events, was amplified by high GRS, of which the genetic variations in PNPLA3, TM6SF2, and MBOAT7 play the principal roles. MAFLD case with normal body weight is also associated with an increased risk of hepatic outcomes, but the genetic factor seems do not influence the risk in this subpopulation.
MAFLD is independently associated with an increased risk of both intrahepatic and extrahepatic events. Fatty liver disease related genetic variants amplify the effect of MAFLD on disease outcomes.
[Display omitted]</description><subject>Cardiovascular Disease</subject><subject>Cirrhosis</subject><subject>Disease Hotspot</subject><subject>Genetic Variants</subject><subject>Humans</subject><subject>Lipase - genetics</subject><subject>Liver Cancer</subject><subject>MAFLD</subject><subject>Membrane Proteins - genetics</subject><subject>NAFLD</subject><subject>Non-alcoholic Fatty Liver Disease - epidemiology</subject><subject>Non-alcoholic Fatty Liver Disease - genetics</subject><subject>Polymorphism, Single Nucleotide</subject><issn>1542-3565</issn><issn>1542-7714</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctuEzEUhi1UREvhAdggL7togq_jibqK0qaNFIqEClvL4zluHM0ltZ1I2fUdEC_Ik-AwaZesfNH3f9I5P0KfKBlTQosv67F9XI0ZYfnNxoTzN-iMSsFGSlFxcrxzWchT9D7GNSFsIibqHTrlnJeqUOQM_X5YAb4D06QVXrQbYxPuHf46nS-vL7HB9_0OGnztI5gIeNZsY4JwIO4HYhHxtN003nmocbXHKdsWXYLHYFL-uXEOBuPcpLTHS7_L8aPuz_Ov79D8426hg-Qt_mmCN12KH9BbZ5oIH4_nOfoxv3mY3Y2W324Xs-lyZLnkaUTBkomznBWFUaWlVCpRm2oCRpHa1K5QrDS8ZLyumJROEiGNoFBRaRUBxvg5uhi8m9A_bSEm3fpooWlMB_02aiaUKIUQpcooHVAb-hgDOL0JvjVhrynRhzb0Wuc29KENTZnObeTM56N-W7VQvyZe1p-BqwGAPOTOQ9DReugs1D7kxem69__R_wXARpn2</recordid><startdate>202204</startdate><enddate>202204</enddate><creator>Liu, Zhenqiu</creator><creator>Suo, Chen</creator><creator>Shi, Oumin</creator><creator>Lin, Chunqing</creator><creator>Zhao, Renjia</creator><creator>Yuan, Huangbo</creator><creator>Jin, Li</creator><creator>Zhang, Tiejun</creator><creator>Chen, Xingdong</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3763-160X</orcidid></search><sort><creationdate>202204</creationdate><title>The Health Impact of MAFLD, a Novel Disease Cluster of NAFLD, Is Amplified by the Integrated Effect of Fatty Liver Disease–Related Genetic Variants</title><author>Liu, Zhenqiu ; Suo, Chen ; Shi, Oumin ; Lin, Chunqing ; Zhao, Renjia ; Yuan, Huangbo ; Jin, Li ; Zhang, Tiejun ; Chen, Xingdong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-1ec09fc3266a78c11574dab9ea70dadf6728a3823db255f5045a41eb15c70e223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Cardiovascular Disease</topic><topic>Cirrhosis</topic><topic>Disease Hotspot</topic><topic>Genetic Variants</topic><topic>Humans</topic><topic>Lipase - genetics</topic><topic>Liver Cancer</topic><topic>MAFLD</topic><topic>Membrane Proteins - genetics</topic><topic>NAFLD</topic><topic>Non-alcoholic Fatty Liver Disease - epidemiology</topic><topic>Non-alcoholic Fatty Liver Disease - genetics</topic><topic>Polymorphism, Single Nucleotide</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Zhenqiu</creatorcontrib><creatorcontrib>Suo, Chen</creatorcontrib><creatorcontrib>Shi, Oumin</creatorcontrib><creatorcontrib>Lin, Chunqing</creatorcontrib><creatorcontrib>Zhao, Renjia</creatorcontrib><creatorcontrib>Yuan, Huangbo</creatorcontrib><creatorcontrib>Jin, Li</creatorcontrib><creatorcontrib>Zhang, Tiejun</creatorcontrib><creatorcontrib>Chen, Xingdong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical gastroenterology and hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Zhenqiu</au><au>Suo, Chen</au><au>Shi, Oumin</au><au>Lin, Chunqing</au><au>Zhao, Renjia</au><au>Yuan, Huangbo</au><au>Jin, Li</au><au>Zhang, Tiejun</au><au>Chen, Xingdong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Health Impact of MAFLD, a Novel Disease Cluster of NAFLD, Is Amplified by the Integrated Effect of Fatty Liver Disease–Related Genetic Variants</atitle><jtitle>Clinical gastroenterology and hepatology</jtitle><addtitle>Clin Gastroenterol Hepatol</addtitle><date>2022-04</date><risdate>2022</risdate><volume>20</volume><issue>4</issue><spage>e855</spage><epage>e875</epage><pages>e855-e875</pages><issn>1542-3565</issn><eissn>1542-7714</eissn><abstract>Metabolic dysfunction-associated fatty liver disease (MAFLD) is a newly proposed disease category that derived from non-alcoholic fatty liver disease. The impact of MAFLD on health events has not been investigated.
UK Biobank participants were diagnosed for whether MAFLD presented at baseline. Five genetic variants (PNPLA3 rs738409 C/G, TM6SF2 rs58542926 C/T, GCKR rs1260326 T/C, MBOAT7 rs641738 C/T, and HSD17B13 rs72613567 T/TA) were integrated into a genetic risk score (GRS). Cox proportional hazard model was used to examine the association of MAFLD with incident diseases.
A total of 160 979 (38.0%, 95% confidence interval [CI] 37.9%, 38.2%) participants out of 423 252 were diagnosed as MAFLD. Compared with participants without MAFLD, MAFLD cases had multivariate adjusted hazard ratio (HR) for liver cancer of 1.59 (95% CI, 1.28, 1.98), cirrhosis of 2.77 (2.29, 3.36), other liver diseases of 2.09 (1.95, 2.24), cardiovascular diseases of 1.39 (1.34, 1.44), renal diseases of 1.56 (1.48, 1.65), and cancers of 1.07 (1.05, 1.10). The impact of MAFLD, especially on hepatic events, was amplified by high GRS, of which the genetic variations in PNPLA3, TM6SF2, and MBOAT7 play the principal roles. MAFLD case with normal body weight is also associated with an increased risk of hepatic outcomes, but the genetic factor seems do not influence the risk in this subpopulation.
MAFLD is independently associated with an increased risk of both intrahepatic and extrahepatic events. Fatty liver disease related genetic variants amplify the effect of MAFLD on disease outcomes.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33387670</pmid><doi>10.1016/j.cgh.2020.12.033</doi><orcidid>https://orcid.org/0000-0003-3763-160X</orcidid></addata></record> |
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| subjects | Cardiovascular Disease Cirrhosis Disease Hotspot Genetic Variants Humans Lipase - genetics Liver Cancer MAFLD Membrane Proteins - genetics NAFLD Non-alcoholic Fatty Liver Disease - epidemiology Non-alcoholic Fatty Liver Disease - genetics Polymorphism, Single Nucleotide |
| title | The Health Impact of MAFLD, a Novel Disease Cluster of NAFLD, Is Amplified by the Integrated Effect of Fatty Liver Disease–Related Genetic Variants |
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