{"id":"https://openalex.org/W7225060985","doi":"https://doi.org/10.64898/2026.10.29.26366887","title":"Human genetic investigation of TMPRSS6 as a therapeutic target for liver disease: efficacy and safety liabilities","display_name":"Human genetic investigation of TMPRSS6 as a therapeutic target for liver disease: efficacy and safety liabilities","publication_year":2026,"publication_date":"2026-11-01","ids":{"openalex":"https://openalex.org/W7225060985","doi":"https://doi.org/10.64898/2026.10.29.26366887"},"language":"en","primary_location":{"id":"doi:10.64898/2026.10.29.26366887","doi":"https://doi.org/10.64898/2026.10.29.26366887","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.29.26366887","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/11/01/2026.10.29.26366887.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.medrxiv.org/content/medrxiv/early/2026/11/01/2026.10.29.26366887.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5014370405","display_name":"Marie\u2010Joe Dib","orcid":"https://orcid.org/0000-0001-7591-5684","observed_orcids":["https://orcid.org/0000-0001-7591-5684"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Marie-Joe Dib","raw_affiliation_strings":["AquilaGen, Nascent Studio Ltd, London, UK;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"AquilaGen, Nascent Studio Ltd, London, UK;","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5007930206","display_name":"Marijana Vujkovi\u0107","orcid":"https://orcid.org/0000-0003-4924-5714","observed_orcids":["https://orcid.org/0000-0003-4924-5714"]},"institutions":[{"id":"https://openalex.org/I4210133394","display_name":"Philadelphia VA Medical Center","ror":"https://ror.org/03j05zz84","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1322918889","https://openalex.org/I2799886695","https://openalex.org/I4210133394","https://openalex.org/I4210147340"]},{"id":"https://openalex.org/I79576946","display_name":"University of Pennsylvania","ror":"https://ror.org/00b30xv10","country_code":"US","type":"education","lineage":["https://openalex.org/I79576946"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Marijana Vujkovic","raw_affiliation_strings":["Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylv;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA; Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; Department of Biostatistics, Epidemiology and Informatics, University of Pennsylv;","institution_ids":["https://openalex.org/I4210133394","https://openalex.org/I79576946"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5153354799","display_name":"Stephen Burgess","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210134973","display_name":"MRC Biostatistics Unit","ror":"https://ror.org/046vje122","country_code":"GB","type":"facility","lineage":["https://openalex.org/I241749","https://openalex.org/I4210087105","https://openalex.org/I4210134973","https://openalex.org/I90344618"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Stephen Burgess","raw_affiliation_strings":["MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, UK;","institution_ids":["https://openalex.org/I4210134973"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047030358","display_name":"Tithi Dutta","orcid":"https://orcid.org/0000-0001-9751-1429","observed_orcids":["https://orcid.org/0000-0001-9751-1429"]},"institutions":[{"id":"https://openalex.org/I6498739","display_name":"Indian Statistical Institute","ror":"https://ror.org/00q2w1j53","country_code":"IN","type":"education","lineage":["https://openalex.org/I6498739"]}],"countries":["IN"],"is_corresponding":false,"raw_author_name":"Tithi Dutta","raw_affiliation_strings":["Human Genetics Unit, Indian Statistical Institute, Kolkata, India.;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Human Genetics Unit, Indian Statistical Institute, Kolkata, India.;","institution_ids":["https://openalex.org/I6498739"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5020053314","display_name":"Ioanna Tzoulaki","orcid":"https://orcid.org/0000-0002-4275-9328","observed_orcids":["https://orcid.org/0000-0002-4275-9328"]},"institutions":[{"id":"https://openalex.org/I206127235","display_name":"Academy of Athens","ror":"https://ror.org/00qsdn986","country_code":"GR","type":"education","lineage":["https://openalex.org/I206127235"]},{"id":"https://openalex.org/I4210093138","display_name":"Biomedical Research Foundation of the Academy of Athens","ror":"https://ror.org/00gban551","country_code":"GR","type":"nonprofit","lineage":["https://openalex.org/I4210093138"]},{"id":"https://openalex.org/I47508984","display_name":"Imperial College London","ror":"https://ror.org/041kmwe10","country_code":"GB","type":"education","lineage":["https://openalex.org/I47508984"]}],"countries":["GB","GR"],"is_corresponding":false,"raw_author_name":"Ioanna Tzoulaki","raw_affiliation_strings":["Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Biomedical Research Foundation, Academy of Athens, Athens, Greece;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Biomedical Research Foundation, Academy of Athens, Athens, Greece;","institution_ids":["https://openalex.org/I206127235","https://openalex.org/I4210093138","https://openalex.org/I47508984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081896930","display_name":"Abbas Dehghan","orcid":"https://orcid.org/0000-0001-6403-016X","observed_orcids":["https://orcid.org/0000-0001-6403-016X"]},"institutions":[{"id":"https://openalex.org/I47508984","display_name":"Imperial College London","ror":"https://ror.org/041kmwe10","country_code":"GB","type":"education","lineage":["https://openalex.org/I47508984"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Abbas Dehghan","raw_affiliation_strings":["Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.;","institution_ids":["https://openalex.org/I47508984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069936360","display_name":"Hanieh Yaghootkar","orcid":"https://orcid.org/0000-0001-9672-9477","observed_orcids":["https://orcid.org/0000-0001-9672-9477"]},"institutions":[{"id":"https://openalex.org/I43439940","display_name":"University of Southampton","ror":"https://ror.org/01ryk1543","country_code":"GB","type":"education","lineage":["https://openalex.org/I43439940"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Hanieh Yaghootkar","raw_affiliation_strings":["School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK; School of Electronics and Computer Science, Faculty of Engineering and Physical Science, University of Southampton, Southampton, UK;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK; School of Electronics and Computer Science, Faculty of Engineering and Physical Science, University of Southampton, Southampton, UK;","institution_ids":["https://openalex.org/I43439940"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5059506792","display_name":"Devendra Meena","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I47508984","display_name":"Imperial College London","ror":"https://ror.org/041kmwe10","country_code":"GB","type":"education","lineage":["https://openalex.org/I47508984"]},{"id":"https://openalex.org/I6498739","display_name":"Indian Statistical Institute","ror":"https://ror.org/00q2w1j53","country_code":"IN","type":"education","lineage":["https://openalex.org/I6498739"]}],"countries":["GB","IN"],"is_corresponding":true,"raw_author_name":"Devendra Meena","raw_affiliation_strings":["Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Human Genetics Unit, Indian Statistical Institute, Kolkata, India"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK; Human Genetics Unit, Indian Statistical Institute, Kolkata, India","institution_ids":["https://openalex.org/I47508984","https://openalex.org/I6498739"]}]}],"institutions":[],"countries_distinct_count":4,"institutions_distinct_count":8,"corresponding_author_ids":["https://openalex.org/A5059506792"],"corresponding_institution_ids":["https://openalex.org/I47508984","https://openalex.org/I6498739"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10351","display_name":"Liver Disease Diagnosis and Treatment","score":0.7724999785423279,"subfield":{"id":"https://openalex.org/subfields/2713","display_name":"Epidemiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10351","display_name":"Liver Disease Diagnosis and Treatment","score":0.7724999785423279,"subfield":{"id":"https://openalex.org/subfields/2713","display_name":"Epidemiology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10452","display_name":"Iron Metabolism and Disorders","score":0.10520000010728836,"subfield":{"id":"https://openalex.org/subfields/2720","display_name":"Hematology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.0778999999165535,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/tmprss6","display_name":"TMPRSS6","score":0.9760000109672546},{"id":"https://openalex.org/keywords/matriptase-2","display_name":"matriptase-2","score":0.9639999866485596},{"id":"https://openalex.org/keywords/hepcidin","display_name":"hepcidin","score":0.9559999704360962},{"id":"https://openalex.org/keywords/iron-homeostasis","display_name":"iron homeostasis","score":0.890999972820282},{"id":"https://openalex.org/keywords/liver-iron-concentration","display_name":"liver iron concentration","score":0.7900000214576721},{"id":"https://openalex.org/keywords/steatohepatitis","display_name":"steatohepatitis","score":0.8410000205039978},{"id":"https://openalex.org/keywords/liver-fibrosis","display_name":"liver fibrosis","score":0.9359999895095825},{"id":"https://openalex.org/keywords/steatosis","display_name":"steatosis","score":0.722000002861023},{"id":"https://openalex.org/keywords/coronary-artery-disease","display_name":"coronary artery disease","score":0.8209999799728394},{"id":"https://openalex.org/keywords/ldl-cholesterol","display_name":"LDL cholesterol","score":0.996999979019165},{"id":"https://openalex.org/keywords/non-alcoholic-fatty-liver-disease","display_name":"non-alcoholic fatty liver disease","score":0.7009999752044678},{"id":"https://openalex.org/keywords/liver-cirrhosis","display_name":"liver cirrhosis","score":0.6840000152587891},{"id":"https://openalex.org/keywords/hepatocellular-carcinoma","display_name":"hepatocellular carcinoma","score":0.9279999732971191},{"id":"https://openalex.org/keywords/therapeutic-target","display_name":"therapeutic target","score":0.5329999923706055},{"id":"https://openalex.org/keywords/mendelian-randomization","display_name":"Mendelian randomization","score":0.8450000286102295}],"concepts":[{"id":"https://openalex.org/C173188278","wikidata":"https://www.wikidata.org/wiki/Q18052595","display_name":"TMPRSS6","level":5,"score":0.6978999972343445},{"id":"https://openalex.org/C2779478299","wikidata":"https://www.wikidata.org/wiki/Q2335423","display_name":"Steatohepatitis","level":4,"score":0.5730999708175659},{"id":"https://openalex.org/C2776768029","wikidata":"https://www.wikidata.org/wiki/Q14882371","display_name":"Hepcidin","level":3,"score":0.5472000241279602},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.4869000017642975},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.48069998621940613},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.46639999747276306},{"id":"https://openalex.org/C2779901538","wikidata":"https://www.wikidata.org/wiki/Q6816584","display_name":"Mendelian randomization","level":5,"score":0.4560000002384186},{"id":"https://openalex.org/C2777214474","wikidata":"https://www.wikidata.org/wiki/Q147778","display_name":"Cirrhosis","level":2,"score":0.42170000076293945},{"id":"https://openalex.org/C2777075537","wikidata":"https://www.wikidata.org/wiki/Q929737","display_name":"Liver disease","level":2,"score":0.3716999888420105},{"id":"https://openalex.org/C2778163477","wikidata":"https://www.wikidata.org/wiki/Q43656","display_name":"Cholesterol","level":2,"score":0.3538999855518341},{"id":"https://openalex.org/C2778213512","wikidata":"https://www.wikidata.org/wiki/Q844935","display_name":"Coronary artery disease","level":2,"score":0.34790000319480896},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3472999930381775},{"id":"https://openalex.org/C2780948078","wikidata":"https://www.wikidata.org/wiki/Q21130010","display_name":"PCSK9","level":5,"score":0.34220001101493835},{"id":"https://openalex.org/C2779102576","wikidata":"https://www.wikidata.org/wiki/Q5113984","display_name":"Chronic liver disease","level":3,"score":0.32339999079704285},{"id":"https://openalex.org/C2778772119","wikidata":"https://www.wikidata.org/wiki/Q6058862","display_name":"Fatty liver","level":3,"score":0.3206999897956848},{"id":"https://openalex.org/C75563809","wikidata":"https://www.wikidata.org/wiki/Q2656896","display_name":"Missense mutation","level":4,"score":0.2953999936580658},{"id":"https://openalex.org/C41260117","wikidata":"https://www.wikidata.org/wiki/Q668064","display_name":"Hepatology","level":2,"score":0.2937999963760376},{"id":"https://openalex.org/C2776175330","wikidata":"https://www.wikidata.org/wiki/Q1365091","display_name":"Steatosis","level":2,"score":0.29030001163482666},{"id":"https://openalex.org/C40209533","wikidata":"https://www.wikidata.org/wiki/Q5147828","display_name":"Colocalization","level":2,"score":0.28949999809265137},{"id":"https://openalex.org/C136935669","wikidata":"https://www.wikidata.org/wiki/Q14912150","display_name":"GDF15","level":2,"score":0.2736999988555908},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.2671999931335449},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.2621000111103058},{"id":"https://openalex.org/C186413461","wikidata":"https://www.wikidata.org/wiki/Q744727","display_name":"Genetic association","level":5,"score":0.25040000677108765}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.10.29.26366887","doi":"https://doi.org/10.64898/2026.10.29.26366887","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.29.26366887","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/11/01/2026.10.29.26366887.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.10.29.26366887","doi":"https://doi.org/10.64898/2026.10.29.26366887","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.10.29.26366887","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/11/01/2026.10.29.26366887.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":"cc-by-nd","license_id":"https://openalex.org/licenses/cc-by-nd","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":1.0}],"study_designs":[{"id":"https://openalex.org/study-designs/observational-study","display_name":"Observational Study"}],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225060985.pdf","grobid_xml":"https://content.openalex.org/works/W7225060985.grobid-xml"},"referenced_works_count":45,"referenced_works":["https://openalex.org/W1977922596","https://openalex.org/W1979307757","https://openalex.org/W1995768948","https://openalex.org/W2012956876","https://openalex.org/W2070165530","https://openalex.org/W2073836327","https://openalex.org/W2118822739","https://openalex.org/W2147647675","https://openalex.org/W2168209462","https://openalex.org/W2563340071","https://openalex.org/W2792063579","https://openalex.org/W2818417770","https://openalex.org/W2951135870","https://openalex.org/W2951144892","https://openalex.org/W2952686929","https://openalex.org/W3014806942","https://openalex.org/W3158487697","https://openalex.org/W3170012751","https://openalex.org/W3175752499","https://openalex.org/W3210406414","https://openalex.org/W4280552086","https://openalex.org/W4281771922","https://openalex.org/W4295569562","https://openalex.org/W4298138773","https://openalex.org/W4310766578","https://openalex.org/W4311455437","https://openalex.org/W4317390883","https://openalex.org/W4361000000","https://openalex.org/W4385577954","https://openalex.org/W4386567042","https://openalex.org/W4387344289","https://openalex.org/W4389232203","https://openalex.org/W4392897378","https://openalex.org/W4399224517","https://openalex.org/W4400770247","https://openalex.org/W4408243472","https://openalex.org/W4408243820","https://openalex.org/W4409007598","https://openalex.org/W4411201689","https://openalex.org/W4411236502","https://openalex.org/W4413104626","https://openalex.org/W4413898654","https://openalex.org/W4417492474","https://openalex.org/W7131873808","https://openalex.org/W7163922155"],"related_works":["https://openalex.org/W2082855795","https://openalex.org/W2974771668","https://openalex.org/W4317797094","https://openalex.org/W4411236502","https://openalex.org/W2981283629","https://openalex.org/W4312218781","https://openalex.org/W1963860082","https://openalex.org/W4310113779","https://openalex.org/W1998483336","https://openalex.org/W2901107918"],"abstract_inverted_index":{"Abstract":[0],"Background":[1],"&":[2],"Aims:":[3],"Disease-modifying":[4],"therapies":[5],"for":[6,27,216],"steatohepatitis":[7],"and":[8,30,81,89,103,109,133,182,203],"fibrosis":[9],"remain":[10],"limited.":[11],"Matriptase-2":[12],"(TMPRSS6),":[13],"a":[14,143],"serine":[15],"protease":[16],"suppressing":[17],"hepcidin":[18,199],"to":[19,45,114,222],"regulate":[20],"iron":[21,28,127,234,258],"homeostasis,":[22],"is":[23],"under":[24],"clinical":[25,90,101,251],"investigation":[26],"overload,":[29],"preclinical":[31],"evidence":[32,231],"suggests":[33],"its":[34],"inhibition":[35,53,121,163],"may":[36,214,254],"attenuate":[37],"metabolic":[38],"liver":[39,75,87,91,126,153,252],"disease.":[40],"Whether":[41],"these":[42],"effects":[43,69],"translate":[44],"humans":[46],"remains":[47],"unknown.":[48],"Methods:":[49],"We":[50],"proxied":[51,119,161],"TMPRSS6":[52,120,162,237],"using":[54],"the":[55,225],"missense":[56],"variant":[57],"rs855791,":[58],"weighted":[59],"on":[60,70,243],"circulating":[61],"hepcidin.":[62],"Using":[63],"Mendelian":[64],"randomization":[65],"(MR),":[66],"we":[67],"assessed":[68],"(1)":[71],"magnetic":[72],"resonance":[73],"imaging-derived":[74],"phenotypes,":[76],"including":[77],"corrected":[78],"T1":[79],"(cT1)":[80],"proton":[82],"density":[83],"fat":[84],"fraction":[85],"(PDFF),":[86],"enzymes":[88],"outcomes;":[92],"(2)":[93],"cardiometabolic":[94],"endpoints;":[95],"(3)":[96],"2,940":[97],"plasma":[98],"proteins;":[99],"(4)":[100],"biomarkers;":[102],"(5)":[104],"2,272":[105],"disease":[106,186],"endpoints.":[107],"Colocalization":[108],"mediation":[110],"analyses":[111],"were":[112],"used":[113],"characterize":[115],"mechanisms.":[116],"Results:":[117],"Genetically":[118,160],"was":[122,149,164],"associated":[123,166],"with":[124,140,151,167,193,198,250],"lower":[125,168],"content":[128],"(\u03b2":[129,136,171,178],"=":[130,137,172,179,190,201,207],"-2.50,":[131],"P<0.001)":[132,181],"higher":[134,175,183],"cT1":[135],"1.59,":[138,191],"P<0.001),":[139,174,192],"colocalization":[141,195],"indicating":[142],"shared":[144],"causal":[145],"signal.":[146],"No":[147],"association":[148],"observed":[150],"PDFF,":[152],"volume,":[154],"NAFLD,":[155],"cirrhosis":[156],"or":[157],"hepatocellular":[158],"carcinoma.":[159],"also":[165],"C-reactive":[169],"protein":[170],"\u22120.17,":[173],"LDL":[176,204,212,269],"cholesterol":[177,205,213],"0.22,":[180],"coronary":[184],"artery":[185],"(CAD)":[187],"risk":[188],"(OR":[189],"weak":[194],"of":[196,224],"CAD":[197,226,264],"(PP.H\u2084":[200,206],"0.56)":[202],"0.48).":[208],"Mediation":[209],"analysis":[210],"suggested":[211],"account":[215],"approximately":[217],"21%":[218],"(95%":[219],"CI":[220],"9%":[221],"34%)":[223],"association.":[227],"Conclusions:":[228],"Human":[229],"genetic":[230],"supports":[232],"hepatic":[233,257],"lowering":[235],"by":[236,268],"inhibition,":[238],"but":[239],"not":[240],"an":[241],"effect":[242],"steatosis.":[244],"Higher":[245],"cT1,":[246],"without":[247],"concordant":[248],"associations":[249],"outcomes,":[253],"reflect":[255],"reduced":[256],"rather":[259],"than":[260],"worsening":[261],"fibroinflammation.":[262],"The":[263],"signal,":[265],"partly":[266],"mediated":[267],"cholesterol,":[270],"warrants":[271],"careful":[272],"consideration":[273],"in":[274],"trial":[275],"design.":[276]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2026-11-02T00:00:00"}