biostudies-literatureGerman JNCATS NIH HHSEuropean Research CouncilNIDDK NIH HHSNIMH NIH HHSEesti Teadusagentuur (Estonian Research Council)NHGRI NIH HHSBroad Institute2269-2276https://www.ebi.ac.uk/biostudies/studies/S-EPMC12283387biostudies-literatureUnknown31(7)Obesity is a major public health challenge. Glucagon-like peptide-1 receptor agonists (GLP1-RA) and bariatric surgery (BS) are effective weight loss interventions; however, the genetic factors influencing treatment response remain largely unexplored. Moreover, most previous studies have focused on race and ethnicity rather than genetic ancestry. Here we analyzed 10,960 individuals from 9 multiancestry biobank studies across 6 countries to assess the impact of known genetic factors on weight loss. Between 6 and 12 months, GLP1-RA users had an average weight change of -3.93% or -6.00%, depending on the outcome definition, with modest ancestry-based differences. BS patients experienced -21.17% weight change between 6 and 48 months. We found no significant associations between GLP1-RA-induced Nature medicineAssociation between plausible genetic factors and weight loss from GLP1-RA and bariatric surgery.PMC12283387R01 MH115676PSG759101117251Eric and Wendy Schmidt Center FellowshipUL1 TR001881R01 HG009120K23 DK131345U01 HG011715Urbut SKutalik ZMohammed SBarry ACorbetta AHail MALee JVainik URipatti SLoos RJFTozzo VSaad CDing YPhilippakis AAbdel-Latif RSzczerbinski LJanucik ACordioli MAl-Sarraj YWang ZNatarajan PEoli ASmit RAJCajuso TGanna AMbarek HGerman JAkinkuolie APasaniuc BHeyne HOLi JHArumae KfalseAssociation between plausible genetic factors and weight loss from GLP1-RA and bariatric surgery.Obesity is a major public health challenge. Glucagon-like peptide-1 receptor agonists (GLP1-RA) and bariatric surgery (BS) are effective weight loss interventions; however, the genetic factors influencing treatment response remain largely unexplored. Moreover, most previous studies have focused on race and ethnicity rather than genetic ancestry. Here we analyzed 10,960 individuals from 9 multiancestry biobank studies across 6 countries to assess the impact of known genetic factors on weight loss. Between 6 and 12 months, GLP1-RA users had an average weight change of -3.93% or -6.00%, depending on the outcome definition, with modest ancestry-based differences. BS patients experienced -21.17% weight change between 6 and 48 months. We found no significant associations between GLP1-RA-induced 2025-01-01T00:00:00Z2025 Jul2026-03-16T08:17:32.203Z2025-08-15T03:06:18.877ZS-EPMC122833874025127310.1038/s41591-025-03645-3