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Publication : Linking traits based on their shared molecular mechanisms.

First Author  Oren Y Year  2015
Journal  Elife Volume  4
PubMed ID  25781485 Mgi Jnum  J:220730
Mgi Id  MGI:5636075 Doi  10.7554/eLife.04346
Citation  Oren Y, et al. (2015) Linking traits based on their shared molecular mechanisms. Elife 4
abstractText  There is growing recognition that co-morbidity and co-occurrence of disease traits are often determined by shared genetic and molecular mechanisms. In most cases, however, the specific mechanisms that lead to such trait-trait relationships are yet unknown. Here we present an analysis of a broad spectrum of behavioral and physiological traits together with gene-expression measurements across genetically diverse mouse strains. We develop an unbiased methodology that constructs potentially overlapping groups of traits and resolves their underlying combination of genetic loci and molecular mechanisms. For example, our method predicts that genetic variation in the Klf7 gene may influence gene transcripts in bone marrow-derived myeloid cells, which in turn affect 17 behavioral traits following morphine injection; this predicted effect of Klf7 is consistent with an in vitro perturbation of Klf7 in bone marrow cells. Our analysis demonstrates the utility of studying hidden causative mechanisms that lead to relationships between complex traits.
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