Elife. 2022 Jul 15;11:e64329.
Understanding how genetic variation shapes a complex trait relies on accurately quantifying both the additive genetic and genotype-environment interaction effects in an age-dependent manner. We used a linear mixed model to quantify diet-dependent genetic contributions to body weight measured through adulthood in diversity outbred female mice under five diets. We observed that heritability of body weight declined with age under all diets, except the 40% calorie restriction diet. We identified 14 loci with age-dependent associations and 19 loci with age- and diet-dependent associations, with many diet-dependent loci previously linked to neurological function and behavior in mice or humans. We found their allelic effects to be dynamic with respect to genomic background, age, and diet, identifying several loci where distinct alleles affect body weight at different ages. These results enable us to more fully understand and predict the effectiveness of dietary intervention on overall health throughout age in distinct genetic backgrounds.
Wright, Kevin M; Deighan, Andrew; Di Francesco, Andrea; Freund, Adam; Jojic, Vladimir; Churchill, Gary; and Raj, Anil, "Age and diet shape the genetic architecture of body weight in diversity outbred mice." (2022). Faculty Research 2022. 110.
The authors acknowledge Madeleine Cule, Anastasia Baryshnikova, Dale Zhang, and Nicholas Bernstein for their comments on the article and reviewing the software developed for all analyses, and Adam Baker for helping with the design of Table 1. The authors would also like to acknowledge Amelie Baud, Andrew Dahl, and an anonymous reviewer for their insightful comments and suggestions that helped greatly improve our article.
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