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Series GSE152708 Query DataSets for GSE152708
Status Public on Jun 18, 2020
Title Systems genetic analysis in Diversity Outbred mice informs human bone mineral density GWAS and identifies Qsox1 as a novel determinant of bone strength
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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 used Diversity Outbred (DO) mice to directly address these limitations by performing the first systems genetics analysis of over 50 complex skeletal phenotypes. We applied a network approach to cortical bone RNA-seq data to discover 46 genes likely to be causal for human BMD GWAS associations, including the novel genes SERTAD4 and GLT8D2. We also performed GWAS in the DO for a wide-range of bone traits and identify Qsox1 as a novel gene influencing cortical bone accrual and bone strength. Our results provide a new perspective on the genetics of osteoporosis and highlight the ability of the mouse to inform human genetics.
Overall design Here, we sequenced total RNA from 192 Diversity Outbred marrow-depleted left femurs.
Contributor(s) Al-Barghouthi B, Mesner L, Calabrese G, Brooks D, Tommasini S, Bouxsein M, Horowitz M, Rosen C, Nguyen K, Haddox S, Farber E, Onengut-Gumuscu S, Pomp D, Farber C
Citation(s) 34099702
Submission date Jun 17, 2020
Last update date Jun 15, 2021
Contact name Basel Al-Barghouthi
Organization name University of Virginia
Lab Farber Lab
Street address P.O. BOX 800717
City Charlottesville
State/province VA
ZIP/Postal code 22908
Country USA
Platforms (1)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (192)
GSM4624208 Femoral homogenate - DO mouse 1
GSM4624209 Femoral homogenate - DO mouse 2
GSM4624210 Femoral homogenate - DO mouse 4
BioProject PRJNA640164
SRA SRP267741

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Supplementary file Size Download File type/resource
GSE152708_gene_counts.csv.gz 7.4 Mb (ftp)(http) CSV
GSE152708_transformed_gene_counts.csv.gz 9.5 Mb (ftp)(http) CSV
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