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Diet reveals hidden genetic associations

Study published in Nature Communications

An international consortium of researchers, coordinated by the Lübeck Institute of Experimental Dermatology (Lübeck, Germany), made major advances in our understanding how genetics and diet impact on complex traits, such as body weight and disease susceptibility.

Using a large cohort of outbred mice they made the following key discoveries: First, they resolved the genetic association of complex traits to single genes. Second, using diet as a co-variate for their genetic association study, they show that diet considerably shifts the genetic association of many complex traits in the mouse, i.e. body weight. Third, when feeding autoimmune disease-prone mice Western diet, disease onset and prevalence is dramatically accelerated, while caloric restriction protected mice from the induction of autoimmune disease. Lastly, diet-induced changes in the gut micro- and mycobiome, preceded clinical disease (lupus) onset. Taken together, their study, which has recently been published in Nature Communications, highlights the importance of including diet in experimental setups for understanding molecular mechanisms associated with complex traits and suggests that the same should be done in human GWAS to avert spurious associations.

In terms of clinical translation, identifying gene-environment (i.e. diet) interactions may help to identify pharmaceutical interventions that are beneficial for a defined subgroup of the population carrying a specific genotype. Moreover, results in the autoimmune-prone mice indicate that dietary regulation of the microbiome is associated with disease development, suggesting that dietary interventions and/or use of probiotics may be used as preventive measures in populations at risk.