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Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line

Vorobyev, Artem
Gupta, Yask
Sezin, Tanya
Koga, Hiroshi
Bartsch, Yannic C
Belheouane, Meriem
Künzel, Sven
Sina, Christian
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Published in Nature communications. 2019, vol. 10, no. 1, 4097
Abstract Phenotypic variation of quantitative traits is orchestrated by a complex interplay between the environment (e.g. diet) and genetics. However, the impact of gene-environment interactions on phenotypic traits mostly remains elusive. To address this, we feed 1154 mice of an autoimmunity-prone intercross line (AIL) three different diets. We find that diet substantially contributes to the variability of complex traits and unmasks additional genetic susceptibility quantitative trait loci (QTL). By performing whole-genome sequencing of the AIL founder strains, we resolve these QTLs to few or single candidate genes. To address whether diet can also modulate genetic predisposition towards a given trait, we set NZM2410/J mice on similar dietary regimens as AIL mice. Our data suggest that diet modifies genetic susceptibility to lupus and shifts intestinal bacterial and fungal community composition, which precedes clinical disease manifestation. Collectively, our study underlines the importance of including environmental factors in genetic association studies.
Keywords AnimalsAnimals, Outbred StrainsAntibodies, Antinuclear/geneticsBacteria/growth & developmentBiodiversityCrosses, GeneticDietFemaleFungi/growth & developmentGenesGenetic Association StudiesGenetic Predisposition to DiseaseLupus Nephritis/genetics/immunologyMaleMiceMicrobiotaPhysical Chromosome MappingQuantitative Trait Loci/geneticsQuantitative Trait, HeritableSpleen/metabolismTranscriptome/geneticsWhole Genome Sequencing
PMID: 31506438
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Research group Mécanismes des pathologies de l'inflammation cutanée (919)
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VOROBYEV, Artem et al. Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line. In: Nature Communications, 2019, vol. 10, n° 1, p. 4097. doi: 10.1038/s41467-019-11952-w https://archive-ouverte.unige.ch/unige:138252

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Deposited on : 2020-07-06

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