Genetic and molecular signatures highlight diverse pathways linking obesity to type 2 diabetes.

Authors

Pascal M Mutie, Tijana Stojanovic, Valeria Lo Faro, Torgny Karlsson, Åsa Johansson

Published in

Nature communications. Volume 17. Issue 1. Jul 08, 2026. Epub Jul 08, 2026.

Abstract

Obesity is a major risk factor for type 2 diabetes, a disease affecting approximately 10% of the global population. Obesity is a heterogeneous condition, with different components exerting distinct, and sometimes opposing, effects on type 2 diabetes risk. Here, we aim to identify molecular mechanisms through which distinct components of obesity influence risk for type 2 diabetes by integrating multi-omics data. We identify SNPs associated with body mass index in males and females and cluster them based on their Mendelian randomisation estimates on type 2 diabetes risk. This analysis reveals four SNP clusters with distinct effects on type 2 diabetes ranging from strongly harmful to protective. We perform cluster-specific two-sample Mendelian randomisation analyses across over 3000 molecular traits to delineate metabolic, lipid, endocrine and glycaemic pathways mediating the harmful and protective effects of distinct obesity components on type 2 diabetes risk.

PMID:
42420302
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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