biostudies-literatureAbner EEC | European Regional Development Fund (Europski Fond za Regionalni Razvoj)Eesti TeadusagentuurMinistry of Education and Research | Estonian Research Competency CouncilMinistry of Education and Research | Estonian Research Competency Council (Research Competency Council)Eesti Teadusagentuur (Estonian Research Council)EC | Horizon 2020 Framework ProgrammeEC | European Regional Development FundEC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020)8956https://www.ebi.ac.uk/biostudies/studies/S-EPMC12508233biostudies-literatureUnknown16(1)Population-specific genome-wide association studies can reveal high-impact genomic variants that influence traits like body-mass index (BMI). Using the Estonian Biobank BMI dataset (n = 204,747 participants) we identified 214 genome-wide significant loci. Among those hits, we identified a common non-coding variant within the newly associated ADGRL3 gene (-0.18 kg/m²; P = 3.21 × 10⁻⁹). Moreover, the missense rare variant PTPRT:p.Arg1384His associated with lower BMI (-0.44 kg/m²; P = 2.51 × 10⁻¹⁰), while the protein-truncating variant POMC:p.Glu206* was associated with considerably higher BMI (+ 0.81 kg/m²; P = 1.48 × 10^-12), both likely affecting the functioning of the leptin-melanocortin pathway. POMC:p.Glu206* was observed in different North-European populations, suggesting a bNature communicationsCharacterization of prevalent genetic variants in the Estonian Biobank body-mass index GWAS.PMC12508233TK218PSG615PRG1291101060011101137154101117251MOBEC008PSG809PRG1911PRG1117PRG1414101080117810645101137201Kisand KHaapaniemi HTillmann TNikopensius TVainik UAlekseienko AVosa UEstonian Biobank Research TeamHaljasmagi LOllila HMKariis HMTaba NEsko TMagi RMetspalu AMilani LMetspalu MRamo JBatool KEriksson ANelis MAbner EHudjashov GLehto KLall KfalseCharacterization of prevalent genetic variants in the Estonian Biobank body-mass index GWAS.Population-specific genome-wide association studies can reveal high-impact genomic variants that influence traits like body-mass index (BMI). Using the Estonian Biobank BMI dataset (n = 204,747 participants) we identified 214 genome-wide significant loci. Among those hits, we identified a common non-coding variant within the newly associated ADGRL3 gene (-0.18 kg/m²; P = 3.21 × 10⁻⁹). Moreover, the missense rare variant PTPRT:p.Arg1384His associated with lower BMI (-0.44 kg/m²; P = 2.51 × 10⁻¹⁰), while the protein-truncating variant POMC:p.Glu206* was associated with considerably higher BMI (+ 0.81 kg/m²; P = 1.48 × 10^-12), both likely affecting the functioning of the leptin-melanocortin pathway. POMC:p.Glu206* was observed in different North-European populations, suggesting a b2025-01-01T00:00:00Z2025 Oct2026-06-04T09:19:59.754Z2026-05-07T03:12:50.899ZS-EPMC125082334106246210.1038/s41467-025-64006-9