Fig. 2

Heatmap visualizing the effects of all genetic and dietary perturbations on obesity-related traits in zebrafish larvae. Numbers in cells are effects of exposure vs. controls expressed in z-scores, so values <−1.96 and > 1.96 reflect effects with p < 0.05. The study is divided into five main parts, examining the effect of: (1) overfeeding in larvae free from CRISPR/Cas9-induced mutations; (2) genetic burden scores comprising the summed number of mutated alleles across the eight (Multiplex score 1) and seven (Multiplex score 2) genes targeted simultaneously. Mutations in each allele are weighted by their predicted effect on protein function. Larvae from both multiplexes are included in the regression analysis and the effect of Multiplex score 1 is adjusted for the weighted effect of mutations in genes targeted in Multiplex 2 and vice versa; (3) the effect of CRISPR/Cas9-induced mutations in zebrafish orthologues of human obesity genes on obesity-related traits in offspring of CRISPR/Cas9 founders of Multiplexes 1 and 2; (4) the effect of CRISPR/Cas9-induced mutations on cardiometabolic outcomes in CRISPR/Cas9 founders targeted at orthologues of one human gene at a time; and (5) the effect of CRISPR/Cas9-induced mutations on food intake in CRISPR/Cas9 founders (AB). * effect of each additional mutated allele weighted by mutations’ predicted effect on protein function in the F₁ generation. ** effect of frameshift and/or premature stop codon-introducing mutations in both alleles vs. no mutated alleles in the F₁ generation. *** effects in CRISPR/Cas9-edited larvae vs. controls in the F₀ generation.