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

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, Stanislav Khil’chenko, 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 Möller, Katja Bieber, John F. Baines, Saleh M. Ibrahim and Ralf J. Ludwig ()
Additional contact information
Artem Vorobyev: University of Lübeck
Yask Gupta: University of Lübeck
Tanya Sezin: University of Lübeck
Hiroshi Koga: University of Lübeck
Yannic C. Bartsch: University of Lübeck and University Medical Center Schleswig-Holstein
Meriem Belheouane: Max Planck Institute for Evolutionary Biology
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
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
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
Saleh M. Ibrahim: University of Lübeck
Ralf J. Ludwig: University of Lübeck

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11952-w

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