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

First Author  Wright KM Year  2022
Journal  Elife Volume  11
PubMed ID  35838135 Mgi Jnum  J:346792
Mgi Id  MGI:7316119 Doi  10.7554/eLife.64329
Citation  Wright KM, et al. (2022) Age and diet shape the genetic architecture of body weight in diversity outbred mice. Elife 11:e64329
abstractText  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.
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