دورية أكاديمية
An atlas of genetic influences on osteoporosis in humans and mice.
| العنوان: | An atlas of genetic influences on osteoporosis in humans and mice. |
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| المؤلفون: | Morris, John A, Kemp, John P, Youlten, Scott E, Laurent, Laetitia, Logan, John G, Chai, Ryan C, Vulpescu, Nicholas A, Forgetta, Vincenzo, Kleinman, Aaron, Mohanty, Sindhu T, Sergio, C Marcelo, Quinn, Julian, Nguyen-Yamamoto, Loan, Luco, Aimee-Lee, Vijay, Jinchu, Simon, Marie-Michelle, Pramatarova, Albena, Medina-Gomez, Carolina, Trajanoska, Katerina, Ghirardello, Elena J, Butterfield, Natalie C, Curry, Katharine F, Leitch, Victoria D, Sparkes, Penny C, Adoum, Anne-Tounsia, Mannan, Naila S, Komla-Ebri, Davide SK, Pollard, Andrea S, Dewhurst, Hannah F, Hassall, Thomas AD, Beltejar, Michael-John G, 23andMe Research Team, Adams, Douglas J, Vaillancourt, Suzanne M, Kaptoge, Stephen, Baldock, Paul, Cooper, Cyrus, Reeve, Jonathan, Ntzani, Evangelia E, Evangelou, Evangelos, Ohlsson, Claes, Karasik, David, Rivadeneira, Fernando, Kiel, Douglas P, Tobias, Jonathan H, Gregson, Celia L, Harvey, Nicholas C, Grundberg, Elin, Goltzman, David, Adams, David J, Lelliott, Christopher J, Hinds, David A, Ackert-Bicknell, Cheryl L, Hsu, Yi-Hsiang, Maurano, Matthew T, Croucher, Peter I, Williams, Graham R, Bassett, JH Duncan, Evans, David M, Richards, J Brent |
| بيانات النشر: | Springer Science and Business Media LLC //dx.doi.org/10.1038/s41588-018-0302-x Nat Genet |
| سنة النشر: | 2019 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | Adult, Aged, Animals, Bone Density, Female, Fractures, Bone, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Mice, Knockout, Middle Aged, Osteoporosis, Phenotype, Polymorphism, Single Nucleotide |
| الوصف: | Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR) = 58, P = 1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P < 0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | Print-Electronic; application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/294653Test |
| DOI: | 10.17863/CAM.41757 |
| الإتاحة: | https://doi.org/10.17863/CAM.41757Test https://www.repository.cam.ac.uk/handle/1810/294653Test |
| حقوق: | All rights reserved |
| رقم الانضمام: | edsbas.72E446A7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.17863/CAM.41757 |
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