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

Author

Listed:
  • Artem Vorobyev

    (University of Lübeck
    University of Lübeck)

  • Yask Gupta

    (University of Lübeck)

  • Tanya Sezin

    (University of Lübeck)

  • Hiroshi Koga

    (University of Lübeck
    Kurume University School of Medicine)

  • Yannic C. Bartsch

    (University of Lübeck and University Medical Center Schleswig-Holstein)

  • Meriem Belheouane

    (Max Planck Institute for Evolutionary Biology
    Kiel University)

  • Sven Künzel

    (Max Planck Institute for Evolutionary Biology)

  • Christian Sina

    (University of Lübeck, Ratzeburger Allee 160)

  • Paul Schilf

    (University of Lübeck)

  • Heiko Körber-Ahrens

    (University of Lübeck
    University Medical Center Goettingen)

  • Foteini Beltsiou

    (University of Lübeck)

  • Anna Lara Ernst

    (University of Lübeck)

  • Stanislav Khil’chenko

    (University of Lübeck)

  • Hassanin Al-Aasam

    (University of Lübeck)

  • Rudolf A. Manz

    (University of Lübeck)

  • Sandra Diehl

    (Goethe University)

  • Moritz Steinhaus

    (University of Lübeck and University Medical Center Schleswig-Holstein)

  • Joanna Jascholt

    (University of Lübeck)

  • Phillip Kouki

    (University of Lübeck)

  • Wolf-Henning Boehncke

    (University of Geneva)

  • Tanya N. Mayadas

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Detlef Zillikens

    (University of Lübeck)

  • Christian D. Sadik

    (University of Lübeck)

  • Hiroshi Nishi

    (Brigham and Women’s Hospital and Harvard Medical School
    University of Tokyo)

  • Marc Ehlers

    (University of Lübeck and University Medical Center Schleswig-Holstein)

  • Steffen Möller

    (Institute for Biostatistics and Informatics in Medicine and Ageing Research)

  • Katja Bieber

    (University of Lübeck)

  • John F. Baines

    (Max Planck Institute for Evolutionary Biology
    Kiel University)

  • Saleh M. Ibrahim

    (University of Lübeck)

  • Ralf J. Ludwig

    (University of Lübeck)

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.

Suggested Citation

  • Artem Vorobyev & Yask Gupta & Tanya Sezin & Hiroshi Koga & Yannic C. Bartsch & Meriem Belheouane & Sven Künzel & Christian Sina & Paul Schilf & Heiko Körber-Ahrens & Foteini Beltsiou & Anna Lara Ernst, 2019. "Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11952-w
    DOI: 10.1038/s41467-019-11952-w
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    Cited by:

    1. Yask Gupta & Anna Lara Ernst & Artem Vorobyev & Foteini Beltsiou & Detlef Zillikens & Katja Bieber & Simone Sanna-Cherchi & Angela M. Christiano & Christian D. Sadik & Ralf J. Ludwig & Tanya Sezin, 2023. "Impact of diet and host genetics on the murine intestinal mycobiome," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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