Gene-diet Interactions Associated with Complex Trait Variation in an Advanced Intercross Outbred Mouse Line

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Sep 12

PMID 31506438

Citations 15

Authors

Artem Vorobyev

Yask Gupta

Tanya Sezin

Hiroshi Koga

Yannic C Bartsch

Meriem Belheouane

Sven Kunzel

Christian Sina

Paul Schilf

Heiko Korber-Ahrens

Foteini Beltsiou

Anna Lara Ernst

Stanislav Khilchenko

Hassanin Al-Aasam

Rudolf A Manz

Sandra Diehl

Moritz Steinhaus

Joanna Jascholt

Phillip Kouki

Wolf-Henning Boehncke

Tanya N Mayadas

Detlef Zillikens

Christian D Sadik

Hiroshi Nishi

Marc Ehlers

Steffen Moller

Katja Bieber

John F Baines

Saleh M Ibrahim

Ralf J Ludwig

Affiliations

Soon will be listed here.

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.

Citing Articles

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Genome-wide mapping of gene-microbe interactions in the murine lung microbiota based on quantitative microbial profiling.

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Impact of diet and host genetics on the murine intestinal mycobiome.

Gupta Y, Ernst A, Vorobyev A, Beltsiou F, Zillikens D, Bieber K Nat Commun. 2023; 14(1):834.

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