(A) Outline of study design. (B) Median (interquartile range) body weight in grams and (C) median (interquartile range) growth rate in grams per day for five dietary treatments from 60 to 660 days …
Body weight and growth rate trends as a function of age. Mice in this study also underwent an array of phenotyping procedures; the age range for metabolic cage phenotyping is highlighted in pink, …
Phenotypic divergence between animal pairs is quantified by the covariance in body weight at 500 days of age. We plot the cumulative density of body weight covariance for all pairs of animals in the …
(A). Comparison of true to that estimated from EMMA (left panel) and G×EMM (right panel). Simulations were run with an equal number of samples in each environment () and with the same value for …
(A) Body weight proportion of phenotypic variance explained by genetics (PVE) (± SE) for 30–660 days of age. Total PVE estimates are derived from the EMMA (light gray) and gene–environment mixed …
PVE (±SE) of (A) Body weight and (B) growth rate, estimated using raw body weight measurements.
PVE (± SE) of (A) Body weight and (B) growth rate, overlayed with the timing of bouts of phenotyping.
(A) PVE (± SE) (left column) and expected phenotypic variance (±SE) (right column) estimated using kinship calculated from founder-of-origin allele probabilities (top row) and biallelic genotypes …
PVE (±SE) of body weight was estimated without imposing any non-negativity constraints on the variance components in the gene–environment mixed mode (G×EMM) model.
PVE (± SE) of body weight was estimated with and without a diagonal constraint on .
Decomposing the total and diet-dependent PVE into contributions from diet terms (diamonds) and contributions from generation terms (x-markers).
(A) Manhattan plots of additive genetic associations and genotype–diet associations on chromosome 6 at multiple ages. (B, D) Fine-mapping loci associated with body weight: diet-independent …
Genetic loci associated with body weight, using G×EMM, at different ages identified under the additive genetic model (subpanels on the left) and genotype–diet interaction model (subpanels on the …
Genetic loci associated with body weight, using EMMA, at different ages identified under the additive genetic model (subpanels on the left) and genotype–diet interaction model (subpanels on the …
(A) Fine-mapping a locus on chromosome 1 associated with body weight under the additive model (left column) and genotype–diet interaction model (right column). Each circle is a biallelic variant, …
(A) Fine-mapping a locus on chromosome 3 associated with body weight under the additive model (left column) and genotype–diet interaction model (right column). Each circle is a biallelic variant, …
(A) Fine-mapping loci, under the interaction model, at 420 days of age. Significant variants are marked as solid circles. Colors denote variants with shared FAPs; ranks 1, 2, and 3 by logarithm of …
(A) Log odds ratio of additive body weight association as a function of age for the lead variant from each founder allele pattern (FAP) group. Red, orange, and yellow colors denote lead variant for …
(A) Manhattan plots of additive genetic associations and genotype–diet associations on chromosome 5 at multiple ages. (B) Fine-mapping a locus associated with body weight in diet-dependent manner at …
For each fine-mapped locus (A-G), we note the location of the variant with the strongest association and the ages at which the genetic association is significant and plot the estimated effect (SE) …
For each locus, we identified the variant with the lowest p-value at any age, the founder allele pattern (FAP) of this variant, the number of significant variants that comprise this lead FAP, the …
FAP position (Mb) | Significant variants | Significant age range (days) | Age-dependent nonlinearity | Lead candidate genes (if ≤3) | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Chrm | Founder Allele Pattern (FAP) | FAP rank | p-Value | Start | End | Total | Open chromatin | ||||
Diet-independent | |||||||||||
1 | AJ/NOD | 1 | 3.24E-05 | ** | 152.046626 | 152.046626 | 1 | 1 | 60 | 1.44E-05 | Trmt1l, Edem3 |
AJ/NOD/129 | 2 | 3.05E-05 | ** | 151.473677 | 152.280212 | 58 | 10 | 60 | — | ||
2 | 129/CAST/PWK | 1 | 2.17E-05 | ** | 77.154962 | 77.357295 | 80 | 8 | 120–360 | 2.83E-09 | Ccdc141, Sestd1 |
3 | AJ/NOD/NZO/CAST | 1 | 1.89E-05 | ** | 50.533599 | 50.595073 | 55 | — | 200–260 | 5.03E-12 | Slc7a11 |
4 | AJ | 1 | 6.81E-06 | *** | 58.950364 | 60.267128 | 5 | 2 | 260–360 | 3.82E-19 | Ugcg |
PWK/WSB | 2 | 2.80E-05 | ** | 59.461248 | 59.981846 | 39 | 3 | 100–300 | — | ||
6 | AJ/NOD | 1 | 2.75E-07 | *** | 53.61761 | 55.555977 | 89 | 2 | 60–200 | 1.55E-26 | Creb5 |
7 | B6/CAST | 1 | 4.20E-06 | *** | 71.375007 | 72.786849 | 47 | 1 | 80–160 | 2.48E-11 | Mctp2 |
7 | AJ/129/NZO/PWK | 1 | 5.70E-06 | *** | 134.08785 | 134.704465 | 20 | 2 | 80–200 | 9.17E-10 | Adam12 |
10 | 129/NZO/PWK/WSB | 1 | 4.99E-06 | *** | 9.078054 | 9.078054 | 1 | — | 540–660 | 9.52E-06 | Samd5 |
129/NZO/WSB | 2 | 2.25E-05 | ** | 8.903387 | 9.092694 | 10 | 2 | 540 | Sash1, Samd5 | ||
10 | CAST/PWK | 1 | 5.98E-06 | *** | 91.163191 | 91.905287 | 2,779 | 81 | 120–660 | 4.09E-10 | Anks1b, Apaf1 |
11 | AJ/NZO/PWK/CAST | 1 | 5.89E-05 | ** | 58.155424 | 58.155424 | 1 | — | 80 | 2.35E-05 | — |
B6/CAST | 2 | 4.91E-05 | ** | 56.985645 | 59.035309 | 603 | 70 | 80–100 | — | ||
12 | NZO/CAST | 1 | 6.47E-05 | ** | 99.520559 | 99.907182 | 43 | 3 | 160–260 | 3.83E-12 | Foxn3 |
15 | B6/129/NZO | 1 | 4.77E-07 | *** | 99.390603 | 99.65295 | 92 | 20 | 260–600 | 1.50E-13 | Aqp2, Aqp5, Aqp6 |
17 | AJ/NOD/WSB | 1 | 8.56E-06 | *** | 6.753277 | 8.85311 | 149 | 11 | 60–420 | 1.23E-10 | Pde10a |
19 | AJ/129/NZO/PWK | 1 | 7.90E-05 | ** | 23.025043 | 23.17612 | 58 | 14 | 80–120 | 4.46E-09 | Trpm3, Klf9 |
Diet-dependent | |||||||||||
1 | NOD/CAST | 1 | 4.89E-04 | * | 151.032114 | 153.716837 | 28 | 3 | 360–660 | 3.32E-04 | — |
2 | AJ/CAST/PWK/WSB | 1 | 7.74E-04 | * | 22.192222 | 22.78664 | 86 | 8 | 480 | 1.32E-04 | — |
2 | PWK | 1 | 3.34E-04 | * | 73.590142 | 75.371564 | 1,672 | 44 | 280–300 | 4.62E-03 | — |
3 | NOD/CAST/PWK/WSB | 1 | 3.87E-05 | ** | 50.184746 | 50.419821 | 5 | — | 420–660 | 7.90E-04 | Slc7a11 |
3 | B6/PWK | 1 | 8.29E-05 | ** | 156.74554 | 156.74554 | 1 | — | 660 | 1.60E-05 | Negr1 |
129/CAST/WSB | 2 | 7.33E-04 | * | 156.133466 | 156.387825 | 170 | 8 | 660 | — | ||
4 | 129/NOD/PWK | 1 | 9.61E-04 | * | 57.696301 | 57.84652 | 10 | 1 | 200 | 5.10E-07 | Palm2, Pakap, Akap2 |
NOD | 2 | 9.76E-04 | * | 57.669827 | 57.669827 | 1 | — | 200 | — | ||
5 | NOD | 1 | 3.88E-05 | ** | 19.213904 | 21.57007 | 153 | 16 | 420–660 | 2.26E-03 | Magi2, Ptpn12 |
5 | PWK | 1 | 5.84E-04 | * | 68.986655 | 70.490341 | 277 | — | 360–480 | 2.28E-03 | Kctd8 |
5 | AJ/129/NOD/WSB | 1 | 4.00E-05 | ** | 117.543498 | 118.050453 | 7 | — | 480–540 | 1.55E-03 | — |
B6/CAST/PWK | 2 | 1.04E-04 | * | 116.797769 | 118.270745 | 69 | 10 | 360–600 | — | ||
6 | B6/CAST/PWK | 1 | 1.04E-04 | * | 54.146132 | 55.452827 | 507 | 101 | 540–660 | 7.51E-04 | Ghrhr |
6 | B6/CAST | 1 | 1.68E-05 | ** | 139.190506 | 140.141694 | 111 | 5 | 240–420 | 9.63E-03 | Pik3c2g |
7 | NZO/PWK | 1 | 9.60E-04 | * | 133.838117 | 133.924023 | 218 | 3 | 420 | 3.19E-07 | Adam12 |
12 | AJ/B6 | 1 | 6.29E-04 | * | 78.06102 | 79.734912 | 10 | 2 | 420–540 | 4.23E-04 | Gphn |
WSB | 2 | 9.84E-04 | * | 78.107988 | 78.932842 | 122 | 8 | 360–420 | Gphn | ||
12 | AJ/CAST/PWK/WSB | 1 | 3.53E-04 | * | 102.447268 | 102.56532 | 43 | 4 | 420–480 | 2.59E-05 | — |
13 | NZO/WSB | 1 | 1.00E-04 | ** | 117.100864 | 118.777463 | 99 | 1 | 200–300 | 1.14E-03 | Fgf10 |
15 | AJ/129/NOD | 1 | 3.52E-04 | * | 10.738034 | 12.040137 | 53 | 4 | 240–300 | 1.27E-04 | — |
17 | B6/129/NZO | 1 | 7.52E-04 | * | 6.755865 | 7.598818 | 26 | 3 | 300–360 | 3.23E-03 | — |
18 | 129/CAST | 1 | 3.86E-04 | * | 71.36087 | 71.58844 | 16 | 1 | 480–540 | 6.92E-03 | Dcc |
19 | AJ/B6/WSB | 1 | 1.24E-04 | * | 21.806665 | 22.051277 | 32 | 1 | 220–300 | 3.54E-03 | — |