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An atlas of genetic determinants of forearm fracture
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research at the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.
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2023 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 55, no 11, p. 1820-1830Article in journal (Refereed) Published
Abstract [en]

Osteoporotic fracture is among the most common and costly of diseases. While reasonably heritable, its genetic determinants have remained elusive. Forearm fractures are the most common clinically recognized osteoporotic fractures with a relatively high heritability. To establish an atlas of the genetic determinants of forearm fractures, we performed genome-wide association analyses including 100,026 forearm fracture cases. We identified 43 loci, including 26 new fracture loci. Although most fracture loci associated with bone mineral density, we also identified loci that primarily regulate bone quality parameters. Functional studies of one such locus, at TAC4, revealed that Tac4–/– mice have reduced mechanical bone strength. The strongest forearm fracture signal, at WNT16, displayed remarkable bone-site-specificity with no association with hip fractures. Tall stature and low body mass index were identified as new causal risk factors for fractures. The insights from this atlas may improve fracture prediction and enable therapeutic development to prevent fractures.

Place, publisher, year, edition, pages
Springer Nature, 2023. Vol. 55, no 11, p. 1820-1830
National Category
Medical Genetics and Genomics Orthopaedics
Identifiers
URN: urn:nbn:se:umu:diva-216783DOI: 10.1038/s41588-023-01527-3ISI: 001093262400002PubMedID: 37919453Scopus ID: 2-s2.0-85175830637OAI: oai:DiVA.org:umu-216783DiVA, id: diva2:1813349
Funder
European Regional Development Fund (ERDF)Swedish National Centre for Research in Sports, 87/06Swedish Society of MedicineThe Kempe Foundations, JCK-1021Knut and Alice Wallenberg Foundation, KAW 2015.0317Swedish Research Council, K20006-72X-20155013Swedish Research Council, 2020-01392Swedish Research Council, 2016-01001Region Västerbotten, VLL:159:33-2007Swedish Association of Local Authorities and Regions, ALFGBG-720331Swedish Association of Local Authorities and Regions, ALFGBG-965235Novo Nordisk Foundation, NNF190C0055250Novo Nordisk Foundation, NNF17OC0027864Novo Nordisk Foundation, NNF17OC0027594Novo Nordisk Foundation, NNF14CC0001Available from: 2023-11-20 Created: 2023-11-20 Last updated: 2025-02-10Bibliographically approved

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Pettersson-Kymmer, Ulrika

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