Characterization of prevalent genetic variants in the Estonian Biobank body-mass index GWAS
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Abstract
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 broader, yet elusive, distribution of this damaging variant. These observations indicate the previously unrecognized roles of the ADGRL3 and PTPRT genes in body weight regulation and suggest an increased prevalence of the POMC :p.Glu206* variant in European populations, offering avenues for developing interventions in obesity management.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Computationally efficient whole-genome regression for quantitative and binary traits
Mbatchou, J., Barnard, L., Backman, J., Marcketta, A., Kosmicki, J. A., Ziyatdinov, A., Benner, C., O’Dushlaine, C., Barber, M., Boutkov, B., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00870-7 · Cited by 1,502 · see citing works
Disease variant prediction with deep generative models of evolutionary data
Frazer, J., Notin, P., Dias, M., Gomez, A., Min, J. K., Brock, K., Gal, Y., & Marks, D. S. (2021) · Nature · doi:10.1038/s41586-021-04043-8 · Cited by 791 · see citing works
Okbay, A., Wu, Y., Wang, N., Jayashankar, H., Bennett, M., Nehzati, S. M., Sidorenko, J., Kweon, H., Goldman, G., Gjorgjieva, T., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01016-z · Cited by 654 · see citing works
Self-citationStereoselective amino acid synthesis by synergistic photoredox-pyridoxal radical biocatalysis
Cheng, L., Li, D., Mai, B. K., Bo, Z., Cheng, L., Liu, P., & Yang, Y. (2023) · Science · doi:10.1126/science.adg2420 · Cited by 253 · see citing works
Critical role of STAT3 in leptin's metabolic actions
Buettner, C., Pocai, A., Muse, E. D., Etgen, A. M., Myers, M. G., & Rossetti, L. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.04.014 · Cited by 228 · see citing works
Stergiakouli, E., Gaillard, R., Tavaré, J. M., Balthasar, N., Loos, R. J., Taal, H. R., Evans, D. M., Rivadeneira, F., St Pourcain, B., Uitterlinden, A. G., et al. (2014) · Obesity · doi:10.1002/oby.20840 · Cited by 90 · see citing works
Melson, E., Miras, A. D., & Papamargaritis, D. (2023) · Clinical Medicine · doi:10.7861/clinmed.2023-0144 · Cited by 46 · cited 1× · see citing works
“Moreover, the potent anti-obesity drug tirzepa-tide partially acts as a GIP analog, highlighting the importance of the incretin pathway in weight regulation 71,72 .”
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- Authors
- Abner, E., Batool, K., Taba, N., Nikopensius, T., Läll, K., Alekseienko, A., Eriksson, A., Rämö, J., Haapaniemi, H., Kariis, H. M., Haljasmägi, L., Võsa, U., Tillmann, T., Vainik, U., Lehto, K., Ollila, H. M., Kisand, K., Estonian Biobank Research Team, Metspalu, A., Metspalu, M., Milani, L., Mägi, R., Esko, T., Nelis, M., Hudjashov, G., & Esko, T.
- Affiliations
- University of Tartu (EE)
- Metrosert (EE)
- University of Helsinki (FI)
- McGill University (CA)
- Corresponding author
- Abner, Erik
- Batool, Kanwal
- ORCID
- Abner, Erik
- Batool, Kanwal
- Taba, Nele
- Nikopensius, Tiit
- Läll, Kristi
- Alekseienko, Anastasiia
- Eriksson, Anders
- Rämö, Joel
- Haapaniemi, Hele
- Kariis, Hanna Maria
- Haljasmägi, Liis
- Võsa, Urmo
- Tillmann, Taavi
- Vainik, Uku
- Lehto, Kelli
- Ollila, Hanna M.
- Kisand, Kai
- Metspalu, Andres
- Metspalu, Mait
- Milani, Lili
- Mägi, Reedik
- Nelis, Mari
- Hudjashov, Georgi
- Venue
- Nature Communications
- Published
- 2025-10-08
- Volume
- 16
- Issue
- 1
- Pages
- 8956-8956
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC12508233
- OpenAlex
- W4414932949
- Cited by
- 2
- References
- 8
- Citations by year
- 2026: 2
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Työväentutkimus Vuosikirja (submittedVersion)
- Funders
- Eesti Teadusagentuur (PRG1291, PRG1414, PRG1911, PSG615, PRG1117, PSG809)
- EC | Horizon 2020 Framework Programme (101137154, 101137201, 101060011, 101080117, 810645, 101117251)
- EC | European Regional Development Fund (MOBEC008)
- Ministry of Education and Research | Estonian Research Competency Council (TK218)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- body mass index, obesity genetics, Estonian Biobank, ADGRL3, PTPRT, proopiomelanocortin, missense mutations, truncating mutations, non-coding variants, leptin-melanocortin pathway, body weight regulation, rare variants, European populations
- MeSH terms
- Adult, Aged, Estonia, Female, Humans, Male, Middle Aged, Obesity, Pro-Opiomelanocortin, Genetic Variation, Body Mass Index, Biological Specimen Banks, Polymorphism, Single Nucleotide, Genome-Wide Association Study
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