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Partitioned polygenic risk scores identify distinct types of metabolic dysfunction-associated steatotic liver disease.
Romeo, Stefano; Jamialahmadi, Oveis; De Vincentis, Antonio; Tavaglione, Federica; Malvestiti, Francesco; Li-Gao, Ruifang; Mancina, Rosellina; Alvarez, Marcus; Gelev, Kyla; Maurotti, Samantha; Vespasiani-Gentilucci, Umberto; Rosendaal, Frits; Kozlitina, Julia; Pajukanta, Päivi; Pattou, François; Valenti, Luca.
Afiliación
  • Romeo S; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg.
  • Jamialahmadi O; University of Gothenburg.
  • De Vincentis A; Operative Unit of Internal Medicine, Fondazione Policlinico Universitario Campus Bio-Medico, Rome, Italy.
  • Tavaglione F; University of Gothenburg.
  • Malvestiti F; University of Milan.
  • Li-Gao R; Leiden University Medical Center.
  • Mancina R; Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Wallenberg Laboratory, University of Gothenburg.
  • Alvarez M; University of California, Los Angeles.
  • Gelev K; David Geffen School of Medicine at UCLA.
  • Maurotti S; Magna Graecia University.
  • Vespasiani-Gentilucci U; Fondazione Policlinico Universitario Campus Bio-Medico.
  • Rosendaal F; Leiden University Medical Center.
  • Kozlitina J; UT Southwestern.
  • Pajukanta P; University of California, Los Angeles.
  • Pattou F; Centre Hospitalier Universitaire de Lille.
  • Valenti L; University of Milan.
Res Sq ; 2024 Feb 06.
Article en En | MEDLINE | ID: mdl-38405802
ABSTRACT
Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses an excess of triglycerides in the liver, which can lead to cirrhosis and liver cancer. While there is solid epidemiological evidence of MASLD coexisting with cardiometabolic disease, several leading genetic risk factors for MASLD do not increase the risk of cardiovascular disease, suggesting no causal relationship between MASLD and cardiometabolic derangement. In this work, we leveraged measurements of visceral adiposity and identified 27 novel genetic loci associated with MASLD. Among these loci, we replicated 6 in several independent cohorts. Next, we generated two partitioned polygenic risk scores (PRS) based on the mechanism of genetic association with MASLD encompassing intra-hepatic lipoprotein retention. The two PRS suggest the presence of at least two distinct types of MASLD, one confined to the liver resulting in a more aggressive liver disease and one that is systemic and results in a higher risk of cardiometabolic disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos