Reference : Joint mouse-human phenome-wide association to test gene function and disease risk.
Scientific journals : Article
Life sciences : Genetics & genetic processes
Joint mouse-human phenome-wide association to test gene function and disease risk.
Wang, Xusheng [> >]
Pandey, Ashutosh K. [> >]
Mulligan, Megan K. [> >]
Williams, Evan mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Mozhui, Khyobeni [> >]
Li, Zhengsheng [> >]
Jovaisaite, Virginija [> >]
Quarles, L. Darryl [> >]
Xiao, Zhousheng [> >]
Huang, Jinsong [> >]
Capra, John A. [> >]
Chen, Zugen [> >]
Taylor, William L. [> >]
Bastarache, Lisa [> >]
Niu, Xinnan [> >]
Pollard, Katherine S. [> >]
Ciobanu, Daniel C. [> >]
Reznik, Alexander O. [> >]
Tishkov, Artem V. [> >]
Zhulin, Igor B. [> >]
Peng, Junmin [> >]
Nelson, Stanley F. [> >]
Denny, Joshua C. [> >]
Auwerx, Johan [> >]
Lu, Lu [> >]
Williams, Robert W. [> >]
Nature communications
Yes (verified by ORBilu)
[en] Animals ; Bone Density/genetics ; Caenorhabditis elegans ; Fumarate Hydratase/genetics/metabolism ; Gene Expression Regulation/physiology ; Gene Library ; Genetic Predisposition to Disease ; Genetic Variation ; Genome-Wide Association Study ; Genomics ; Humans ; Mice ; Mice, Inbred DBA ; Quantitative Trait Loci
[en] Phenome-wide association is a novel reverse genetic strategy to analyze genome-to-phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for approximately 5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open-access phenome consisting of approximately 4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets--by far the largest coherent phenome for any experimental cohort ( We tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human.

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