Document Type

Article

Publication Date

7-15-2022

Publication Title

Elife

Keywords

JMG

JAX Source

Elife. 2022 Jul 15;11:e64329.

Volume

11

First Page

e64329

ISSN

2050-084X

PMID

35838135

DOI

https://doi.org/10.7554/elife.64329

Abstract

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.

Comments

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.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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