| Title: | Assessment of the genetic and clinical determinants of hip fracture risk: Genome-wide association and Mendelian randomization study |
| Journal: | Cell Reports Medicine |
| Published: | 18 Oct 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36260985/ |
| DOI: | https://doi.org/10.1016/j.xcrm.2022.100776 |
| URL: | http://www.cell.com/article/S2666379122003317/pdf |
Publication 10601
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Abstract
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.</p>
18 Authors
- Maria Nethander
- Eivind Coward
- Ene Reimann
- Louise Grahnemo
- Maiken E. Gabrielsen
- Carl Wibom
- Estonian Biobank Research Team
- Mari Nelis
- Lili Milani
- Tõnu Esko
- Andres Metspalu
- Reedik Mägi
- Thomas Funck-Brentano
- Mari Hoff
- Arnulf Langhammer
- Ulrika Pettersson-Kymmer
- Kristian Hveem
- Claes Ohlsson
1 Application
| Application ID | Title |
|---|---|
| 51784 | Genetic markers and biomarkers for age-related diseases |
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