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Furthermore, whether these mechanistic pathways are shared across ethnic groups has not been explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a two-step Mendelian randomization (MR) using European-based summary statistics from genome-wide association studies of childhood body mass index (BMI) (n\u2009=\u200961\u00a0111), adulthood proteomics (n\u2009=\u200935\u00a0559), and later life T2D (cases: 242\u00a0283; controls: 1\u00a0569\u00a0734). We also conducted a recall-by-genotype (RbG) study in a Chinese birth cohort (n\u2009=\u2009250) to assess whether childhood BMI was associated with the identified proteomic signals in an East Asian population. Analyses included multi-instrument MR methods (inverse variance weighted and MR-Egger) and, for single-instrument proteins, cis-MR using the Wald ratio, with colocalization validation. Multiple testing was adjusted using false discovery rate (FDR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Higher genetically predicted childhood BMI was associated with 1299 proteins (FDR-adjusted P\u2009&amp;lt;\u2009.05), of which 36 proteins were associated with higher T2D risk. Six proteins were supported by colocalization (PPH4 &amp;gt; 80%). Genetically predicted higher childhood BMI was positively associated with GCKR, RBP1, ENTPD6, and GST A1-1, and inversely associated with PRSS27 and SHBG. The proportion of the BMI-T2D effect mediated by these proteins ranged from 1.87% to 12.92%. However, only SHBG was replicated in Asians in the RbG study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study identified putative actionable proteins that could reduce the elevated T2D risk attributable to childhood adiposity in Europeans, but their relevance in Asian populations requires further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ije\/dyag165","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:45:38Z","timestamp":1785930338000},"source":"Crossref","is-referenced-by-count":0,"title":["Elucidating the proteomic pathways linking childhood body mass index with type 2 diabetes: a Mendelian randomization and recall-by-genotype study"],"prefix":"10.1093","volume":"55","author":[{"given":"Siyu","family":"Chen","sequence":"first","affiliation":[{"name":"School of Public Health, Li Ka Shing Faculty 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