Article (Scientific journals)
Joint mouse-human phenome-wide association to test gene function and disease risk.
Wang, Xusheng; Pandey, Ashutosh K.; Mulligan, Megan K. et al.
2016In Nature Communications, 7, p. 10464
Peer Reviewed verified by ORBi


Full Text
Publisher postprint (2.43 MB)

All documents in ORBilu are protected by a user license.

Send to


Keywords :
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
Abstract :
[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.
Disciplines :
Genetics & genetic processes
Author, co-author :
Wang, Xusheng
Pandey, Ashutosh K.
Mulligan, Megan K.
Williams, Evan  ;  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.
More authors (16 more) Less
External co-authors :
Language :
Title :
Joint mouse-human phenome-wide association to test gene function and disease risk.
Publication date :
Journal title :
Nature Communications
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
Pages :
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 11 May 2020


Number of views
42 (1 by Unilu)
Number of downloads
26 (0 by Unilu)

Scopus citations®
Scopus citations®
without self-citations
WoS citations


Similar publications

Contact ORBilu