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.

Details

Title
Gene-diet interactions associated with complex trait variation in an advanced intercross outbred mouse line
Author
Vorobyev, Artem 1 ; Gupta, Yask 2 ; Sezin, Tanya 3 ; Koga, Hiroshi 4   VIAFID ORCID Logo  ; Bartsch, Yannic C 5 ; Belheouane, Meriem 6 ; Künzel, Sven 7 ; Sina, Christian 8 ; Schilf, Paul 2 ; Körber-Ahrens, Heiko 9 ; Beltsiou, Foteini 2   VIAFID ORCID Logo  ; Anna Lara Ernst 2   VIAFID ORCID Logo  ; Stanislav Khil’chenko 2   VIAFID ORCID Logo  ; Al-Aasam, Hassanin 2   VIAFID ORCID Logo  ; Manz, Rudolf A 10   VIAFID ORCID Logo  ; Diehl, Sandra 11 ; Steinhaus, Moritz 5 ; Jascholt, Joanna 2 ; Kouki, Phillip 2 ; Wolf-Henning Boehncke 12 ; Mayadas, Tanya N 13 ; Zillikens, Detlef 3   VIAFID ORCID Logo  ; Sadik, Christian D 3   VIAFID ORCID Logo  ; Nishi, Hiroshi 14 ; Ehlers, Marc 5   VIAFID ORCID Logo  ; Möller, Steffen 15   VIAFID ORCID Logo  ; Bieber, Katja 2   VIAFID ORCID Logo  ; Baines, John F 6 ; Ibrahim, Saleh M 2 ; Ludwig, Ralf J 2   VIAFID ORCID Logo 

 Lübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany; Department of Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany 
 Lübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany 
 Department of Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany 
 Lübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany; Department of Dermatology, Kurume University School of Medicine, Kurume, Fukuoka, Japan 
 Laboratories of Immunology and Antibody Glycan Analysis, Institute for Nutritional Medicine, University of Lübeck and University Medical Center Schleswig-Holstein, Lübeck, Germany 
 Max Planck Institute for Evolutionary Biology, Plön, Germany; Institute for Experimental Medicine, Kiel University, Kiel, Germany 
 Max Planck Institute for Evolutionary Biology, Plön, Germany 
 Institute of Nutritional Medicine, Molecular Gastroenterology, University of Lübeck, Ratzeburger Allee 160, Lübeck, Germany 
 Lübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Lübeck, Germany; Department of Urology, University Medical Center Goettingen, Goettingen, Germany 
10  Institute for Systemic Inflammation Research, University of Lübeck, Lübeck, Germany 
11  Department of Dermatology, Venereology and Allergology, Goethe University, Frankfurt am Main, Germany 
12  Divison of Dermatology and Venereology, Geneva University Hospitals, and Department of Pathology and Immunology, University of Geneva, Genève, Switzerland 
13  Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA 
14  Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA; Department of Nephrology and Endocrinology, University of Tokyo, Tokyo, Japan 
15  Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University of Rostock, Germany 
Pages
1-15
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2287989724
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.