Parent-of-origin effects propagate through networks to shape metabolic traits

• DOI: 10.7554/elife.72989
• Publication Date: 2022-03-31T12:01:33Z
• Authors: Juan F Macias-Vel...; Celine L St Pierre; Jessica P Wayhart; Li Yin; Larry Spears; Mario A Miranda; Caryn Carson; Katsuhiko Funai; James M Cheverud; Clay F Semenkovich; Heather A Lawson
• Keywords: Epistasis; Genomic Imprinting; Genetic architecture; Inbred strain

Parent-of-origin effects are unexpectedly common in complex traits, including metabolic and neurological traits. can be modified by the environment, but architecture of these gene-by-environmental on phenotypes remains to unraveled. Previously, quantitative trait loci (QTL) showing context-specific parent-of-origin traits were mapped F 16 generation an advanced intercross between LG/J SM/J inbred mice. However, QTL not enriched for known imprinted genes, suggesting another mechanism is needed explain phenomena. We propose that non-imprinted genes generate through interactions with genes. Here, we employ data from mouse populations at different levels intercrossing (F 0 , 1 2 ) lines test this hypothesis. Using multiple incorporating genetic, genomic, physiological data, leverage orthogonal evidence identify networks which propagate. a network comprised three six show effects. This epistatic forms nutritional responsive pathway comprising it jointly serve cellular functions associated growth. focus two Nnat F2r whose interaction associates serum glucose across generations high-fat-fed females. Single-cell RNAseq reveals expression increases decreases pre-adipocytes along adipogenic trajectory, result consistent our observations bulk white adipose tissue.