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Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength
- Source :
- Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-19 (2021)
- Publication Year :
- 2021
- Publisher :
- Nature Publishing Group UK, 2021.
-
Abstract
- Genome-wide association studies (GWASs) for osteoporotic traits have identified over 1000 associations; however, their impact has been limited by the difficulties of causal gene identification and a strict focus on bone mineral density (BMD). Here, we use Diversity Outbred (DO) mice to directly address these limitations by performing a systems genetics analysis of 55 complex skeletal phenotypes. We apply a network approach to cortical bone RNA-seq data to discover 66 genes likely to be causal for human BMD GWAS associations, including the genes SERTAD4 and GLT8D2. We also perform GWAS in the DO for a wide-range of bone traits and identify Qsox1 as a gene influencing cortical bone accrual and bone strength. In this work, we advance our understanding of the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics.<br />Osteoporosis GWAS faces two challenges, causal gene discovery and a lack of phenotypic diversity. Here, the authors use the Diversity Outbred mouse population to inform human GWAS using networks and map genetic loci for 55 bone traits, identifying new potential bone strength genes.
- Subjects :
- 0301 basic medicine
Collaborative Cross Mice
Male
Osteoporosis
General Physics and Astronomy
Datasets as Topic
Genome-wide association study
Genome-wide association studies
Mice
0302 clinical medicine
Bone Density
Osteogenesis
Oxidoreductases Acting on Sulfur Group Donors
Femur
RNA-Seq
Bone mineral
Mice, Knockout
education.field_of_study
Multidisciplinary
Cell Differentiation
Genomics
Fluoresceins
medicine.anatomical_structure
Female
Single-Cell Analysis
Science
Population
Computational biology
Biology
General Biochemistry, Genetics and Molecular Biology
Article
03 medical and health sciences
medicine
Animals
Humans
education
Genetic association
Fluorescent Dyes
Osteoblasts
Glycosyltransferases
Mesenchymal Stem Cells
General Chemistry
medicine.disease
Human genetics
Computational biology and bioinformatics
030104 developmental biology
Cortical bone
human activities
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....029e988d0a2ce207e8fcf9ea1dbb20b7