학술논문
An atlas of genetic determinants of forearm fracture.
Document Type
Academic Journal
Author
Nethander M; 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.; Movérare-Skrtic S; 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.; Kämpe A; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Coward E; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.; Reimann E; Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.; Grahnemo L; 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.; Borbély É; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.; National Laboratory for Drug Research and Development, Budapest, Hungary.; Helyes Z; Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Pécs, Hungary.; National Laboratory for Drug Research and Development, Budapest, Hungary.; Eotvos Lorand Research Network, Chronic Pain Research Group, University of Pécs, Pécs, Hungary.; Funck-Brentano T; BIOSCAR UMRS 1132, Université Paris Diderot, Sorbonne Paris Cité, INSERM, Paris, France.; Cohen-Solal M; BIOSCAR UMRS 1132, Université Paris Diderot, Sorbonne Paris Cité, INSERM, Paris, France.; Tuukkanen J; Department of Anatomy and Cell Biology, Faculty of Medicine, Institute of Cancer Research and Translational Medicine, University of Oulu, Oulu, Finland.; Koskela A; Department of Anatomy and Cell Biology, Faculty of Medicine, Institute of Cancer Research and Translational Medicine, University of Oulu, Oulu, Finland.; Wu J; 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.; Li L; 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.; Lu T; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.; Gabrielsen ME; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.; Mägi R; Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.; Hoff M; Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway.; Department of Rheumatology, St Olavs Hospital, Trondheim, Norway.; Lerner UH; 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.; Henning P; 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.; Ullum H; Statens Serum Institut, Copenhagen, Denmark.; Erikstrup C; Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.; Brunak S; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Langhammer A; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Tuomi T; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.; Folkhälsan Research Center, Helsinki, Finland.; Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, Sweden.; Department of Endocrinology, Abdominal Center, Helsinki University Hospital, Helsinki, Finland.; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Oddsson A; deCODE genetics, Reykjavik, Iceland.; Stefansson K; deCODE genetics, Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.; Pettersson-Kymmer U; Department of Integrative Medical Biology, Clinical Pharmacology, Umea University, Umea, Sweden.; Ostrowski SR; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Immunology, Copenhagen Hospital Biobank Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.; Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.; Pedersen OBV; Department of Clinical Medicine, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.; Department of Clinical Immunology, Zealand University Hospital, Koege, Denmark.; Styrkarsdottir U; deCODE genetics, Reykjavik, Iceland.; Mäkitie O; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.; Folkhälsan Institute of Genetics, Helsinki, Finland.; Children's Hospital and Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Hveem K; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.; HUNT Research Centre, Department of Public Health and Nursing, Norwegian University of Science and Technology, and Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.; Richards JB; Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada.; Department of Human Genetics, McGill University, Montreal, Quebec, Canada.; Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.; Ohlsson C; 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. claes.ohlsson@medic.gu.se.; Region Västra Götaland, Sahlgrenska University Hospital, Department of Drug Treatment, Gothenburg, Sweden. claes.ohlsson@medic.gu.se.
Source
Publisher: Nature Pub. Co Country of Publication: United States NLM ID: 9216904 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1718 (Electronic) Linking ISSN: 10614036 NLM ISO Abbreviation: Nat Genet Subsets: MEDLINE
Subject
Language
English
Abstract
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.
(© 2023. The Author(s).)
(© 2023. The Author(s).)