Lübeck Institute of Experimental Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Department of Dermatology and Center for Research on Inflammation of the Skin, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.
Nat Commun. 2019 Sep 10;10(1):4097. doi: 10.1038/s41467-019-11952-w.
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.
表型性状的表型变异是由环境（例如饮食）和遗传之间的复杂相互作用协调的。然而，基因-环境相互作用对表型性状的影响在很大程度上仍然难以捉摸。为了解决这个问题，我们给 1154 只自身免疫倾向的杂交系（AIL）老鼠喂食三种不同的饮食。我们发现，饮食大大增加了复杂性状的可变性，并揭示了额外的遗传易感性数量性状基因座（QTL）。通过对 AIL 创始株进行全基因组测序，我们将这些 QTL 解析为少数或单个候选基因。为了研究饮食是否也可以调节对特定性状的遗传易感性，我们让 NZM2410/J 老鼠采用与 AIL 老鼠相似的饮食方案。我们的数据表明，饮食可以改变狼疮的遗传易感性，并改变肠道细菌和真菌群落组成，这先于临床疾病表现。总的来说，我们的研究强调了在遗传关联研究中纳入环境因素的重要性。
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