RT Journal Article
SR Electronic
T1 Systems genetics analyses in Diversity Outbred mice inform human bone mineral density GWAS and identify <em>Qsox1</em> as a novel determinant of bone strength
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.24.169839
DO 10.1101/2020.06.24.169839
A1 Basel Al-Barghouthi
A1 Larry D. Mesner
A1 Gina M. Calabrese
A1 Daniel Brooks
A1 Steve M. Tommasini
A1 Mary L. Bouxsein
A1 Mark C. Horowitz
A1 Clifford J. Rosen
A1 Kevin Nguyen
A1 Samuel Haddox
A1 Emily A. Farber
A1 Suna Onengut-Gumuscu
A1 Daniel Pomp
A1 Charles R. Farber
YR 2020
UL http://biorxiv.org/content/early/2020/06/24/2020.06.24.169839.abstract
AB 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 identified 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.Competing Interest StatementThe authors have declared no competing interest.