Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study.

Male Female Humans Genome-Wide Association Study Mendelian Randomization Analysis Bone Density / genetics Hip Fractures / epidemiology Femur Neck
bone mineral density genome-wide association study hip fracture mendelian randomization

Journal

Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894

Informations de publication

Date de publication:
18 10 2022
Historique:
received: 07 03 2022
revised: 07 06 2022
accepted: 19 09 2022
entrez: 19 10 2022
pubmed: 20 10 2022
medline: 22 10 2022
Statut: ppublish

Résumé

Hip fracture is the clinically most important fracture, but the genetic architecture of hip fracture is unclear. Here, we perform a large-scale hip fracture genome-wide association study meta-analysis and Mendelian randomization study using five cohorts from European biobanks. The results show that five genetic signals associate with hip fractures. Among these, one signal associates with falls, but not with bone mineral density (BMD), while four signals are in loci known to be involved in bone biology. Mendelian randomization analyses demonstrate a strong causal effect of decreased femoral neck BMD and moderate causal effects of Alzheimer's disease and having ever smoked regularly on risk of hip fractures. The substantial causal effect of decreased femoral neck BMD on hip fractures in both young and old subjects and in both men and women supports the use of change in femoral neck BMD as a surrogate outcome for hip fractures in clinical trials.

Identifiants

DOI: 10.1016/j.xcrm.2022.100776 PMID: 36260985 PMC: PMC9589021
pubmed: 36260985
pii: S2666-3791(22)00331-7
doi: 10.1016/j.xcrm.2022.100776
pmc: PMC9589021
pii:
doi:

Types de publication

Meta-Analysis Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

100776

Subventions

Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom

Investigateurs

Mari Nelis (M)
Lili Milani (L)
Tõnu Esko (T)
Andres Metspalu (A)

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

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Auteurs

Maria 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, Vita Stråket 11, 41345 Gothenburg, Sweden; Bioinformatics Core Facility, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Eivind Coward (E)

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, 7491 Trondheim, Norway.

Ene Reimann (E)

Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23b, 51010 Tartu, Estonia.

Louise 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, Vita Stråket 11, 41345 Gothenburg, Sweden.

Maiken E Gabrielsen (ME)

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, 7491 Trondheim, Norway.

Carl Wibom (C)

Department of Radiation Sciences, Oncology, Umea University, Umea, Sweden.

Reedik Mägi (R)

Estonian Genome Center, Institute of Genomics, University of Tartu, Riia 23b, 51010 Tartu, Estonia.

Thomas Funck-Brentano (T)

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, Vita Stråket 11, 41345 Gothenburg, Sweden; Department of Rheumatology, Lariboisière Hospital, INSERM U1132, Université de Paris, Paris, France.

Mari Hoff (M)

Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology, Trondheim, Norway; Department of Rheumatology, St Olavs Hospital, Trondheim, Norway.

Arnulf Langhammer (A)

HUNT Research Centre, Forskningsveien 2, 7600 Levanger, Norway"; Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.

Ulrika Pettersson-Kymmer (U)

Department of Integrative Medical Biology, Clinical Pharmacology, Umea University, Umea, Sweden.

Kristian Hveem (K)

K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, 7491 Trondheim, Norway; HUNT Research Centre, Forskningsveien 2, 7600 Levanger, Norway"; Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.

Claes 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, Vita Stråket 11, 41345 Gothenburg, Sweden; Region Västra Götaland, Department of Drug Treatment, Sahlgrenska University Hospital, Gothenburg, Sweden. Electronic address: claes.ohlsson@medic.gu.se.

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Classifications MeSH

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