Accounting for diet and age

Abstract

The diet and age of mice can modulate how different genetic variants impact body weight, demonstrating the need to take context into account when performing genetic studies.

Keywords: diversity outbred mice; gene-environment interaction; genetics; genomics; heritability; longitudinal; mixed models; mouse; quantitative trait locus.

Figure 1.. Schematic representation of diet- and age-dependent genetic effects.

The effect of founder haplotypes on body weight can be diet-dependent (A) or age-dependent (B). In this figure, for simplicity, there are two haplotypes at each locus: purple (upper) and orange (lower) for the variant in (A); and green (upper) and blue (lower) for the variant in (B). In reality, however, there are eight different haplotypes at each locus in the mice studied by Wright et al. The haplotypes in (A) have an effect on body weight only when the mice are fed a caloric-restricted diet (bottom). In this situation, the purple haplotype leads to lower weight. This indicates that the haplotypes have a diet-dependent effect. Similarly, the haplotypes in (B) have an effect on body weight only after 120 days of age, when the green haplotype (top) causes increased body weight.