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

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...

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Detalles Bibliográficos
Autores principales: Nethander, Maria, Coward, Eivind, Reimann, Ene, Grahnemo, Louise, Gabrielsen, Maiken E., Wibom, Carl, Mägi, Reedik, Funck-Brentano, Thomas, Hoff, Mari, Langhammer, Arnulf, Pettersson-Kymmer, Ulrika, Hveem, Kristian, Ohlsson, Claes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9589021/
https://www.ncbi.nlm.nih.gov/pubmed/36260985
http://dx.doi.org/10.1016/j.xcrm.2022.100776
Descripción
Sumario: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.