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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\u00a03000 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.<\/jats:p>","DOI":"10.1038\/s41467-026-74675-9","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T09:04:08Z","timestamp":1783501448000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic and molecular signatures highlight diverse pathways linking obesity to type 2 diabetes"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2626-1703","authenticated-orcid":false,"given":"Pascal M.","family":"Mutie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0613-8539","authenticated-orcid":false,"given":"Tijana","family":"Stojanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4931-7327","authenticated-orcid":false,"given":"Valeria","family":"Lo Faro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8095-6149","authenticated-orcid":false,"given":"Torgny","family":"Karlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2915-4498","authenticated-orcid":false,"given":"\u00c5sa","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,8]]},"reference":[{"key":"74675_CR1","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0140-6736(23)01301-6","volume":"402","author":"KL Ong","year":"2023","unstructured":"Ong, K. 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