{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:22:12Z","timestamp":1791645732897,"version":"4.3.4"},"reference-count":67,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T00:00:00Z","timestamp":1728259200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The prevalence of metabolic dysfunction\u2010associated steatotic liver disease (MASLD) has increased exponentially over the past three decades, in parallel with the global rise in obesity and type 2 diabetes. It is currently the most common cause of liver\u2010related morbidity and mortality. Although obesity has been identified as a key factor in the increased prevalence of MASLD, individual differences in susceptibility are significantly influenced by genetic factors.\n                    <jats:italic>PNPLA3<\/jats:italic>\n                    I148M (rs738409 C&gt;G) is the variant with the greatest impact on the risk of developing progressive MASLD and likely other forms of steatotic liver disease. This variant is prevalent across the globe, with the risk allele (G) frequency exhibiting considerable variation. Here, we review the contribution of\n                    <jats:italic>PNPLA3<\/jats:italic>\n                    I148M to global burden and regional differences in MASLD prevalence, focusing on recent evidence emerging from population\u2010based sequencing studies and prevalence assessments. We calculated the population attributable fraction (PAF) as a means of quantifying the impact of the variant on MASLD. Furthermore, we employ quantitative trait locus (QTL) analysis to ascertain the associations between rs738409 and a range of phenotypic traits. This analysis suggests that these QTLs may underpin pleiotropic effects on extrahepatic traits. Finally, we outline potential avenues for further research and identify key areas for investigation in future studies.\n                  <\/jats:p>","DOI":"10.1111\/liv.16123","type":"journal-article","created":{"date-parts":[[2024,10,7]],"date-time":"2024-10-07T06:09:23Z","timestamp":1728281363000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":54,"title":["Global Epidemiological Impact of\n                    <scp>\n                      <i>PNPLA3<\/i>\n                      I148M\n                    <\/scp>\n                    on Liver Disease"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7720-2290","authenticated-orcid":false,"given":"Julia","family":"Kozlitina","sequence":"first","affiliation":[{"name":"Eugene McDermott Center for Human Growth and Development University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5929-5470","authenticated-orcid":false,"given":"Silvia","family":"Sookoian","sequence":"additional","affiliation":[{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET)  Buenos Aires Argentina"},{"name":"Clinical and Molecular Hepatology, Translational Health Research Center (CENITRES) Maim\u00f3nides University  Buenos Aires Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,7]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000004"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20101253(22)00317\u2010X"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.06.021"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.05.036"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2016.0109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32774"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20466"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572\u20100241.2002.05795.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2004.04059.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.257"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24283"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26767"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.011"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.488"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24017"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24123"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26445"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.038"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.15738"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.10.048"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.023"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2023.04.015"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15852"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.08.025"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.109"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i17.4987"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2014.08.037"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.30251"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15394"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010023\u201006045\u20100"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.11.010"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15268"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.04.047"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.02.007"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3786"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26440"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddab096"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010024\u201001720\u2010y"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31238"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15322"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28370"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3855"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2020.08.054"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010023\u201002553\u20108"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000001072"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32491"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103858"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1712191"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.14309\/ctg.0000000000000400"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.14495"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4216451"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz1776"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010021\u201000913\u2010z"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab614"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i4.305"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publis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