Age and diet shape the genetic architecture of body weight in diversity outbred mice

Vladimir Jojic

Abstract:

Understanding how genetic variation shapes a complex trait relies on accurately
quantifying both the additive genetic and genotype–environment interaction effects in an agedependent 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.