Profiling the genome and proteome of metabolic dysfunction-associated steatotic liver disease identifies potential therapeutic targets.

ABSTRACT:

Background & aims

Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 25% of the population and currently has no effective treatments. Plasma proteins with causal evidence may represent promising drug targets. We aimed to identify plasma proteins in the causal pathway of MASLD and explore their interaction with obesity.

Methods

We analysed 2,941 plasma proteins in 43,978 European participants from UK Biobank. We performed genome-wide association study (GWAS) for all MASLD-associated proteins and created the largest MASLD GWAS (109,885 cases/1,014,923 controls). We performed Mendelian Randomization (MR) and integrated proteins and their encoding genes in MASLD ranges to identify candidate causal proteins. We then validated them through independent re

SUBMITTER: Liu J 

PROVIDER: S-EPMC10705663 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature