Extended Data Fig. 7: Type-A and Type-B UPV show specific metabolic and molecular profiles.
From: Independent phenotypic plasticity axes define distinct obesity sub-types
a, UMAP projection of MZ cotwin couples form the TwinsUK (n = 153), according to 35 morphometric discordances. Each dot represents a cotwin pair, colored by their serum insulin level discordance (calculated as the difference between log-transformed measurements). The different shapes of the cotwin pairs represented the identified groups. Dotted red/green lines highlight the Type-A and Type-B UPV and show the increase insulin levels (that is, relative hyperinsulinemia) in Type-B ‘heavy’ cotwins. b,c, Scatterplots showing the correlation between BMI and insulin level (b) or the HDAC-signature expression (c), in the indicated cotwin groups. Both showing stronger correlation in the Type-B UPV cotwins (BMI/insulin: R2 = 0.51, p-value=2.4-13, BMI/insulin: R2 = 0.57, p-value=4-16). R2 and p-values as calculated by fitted linear regression models. d, Gene set enrichment analysis (GSEA) results of HDAC-related gene sets between the ‘light’ and ‘heavy’ cotwins, belonging to the Type-B UPV group. Gene sets specifically enriched in ‘heavy’ cotwins of the Type-B UPV cluster are shown. NES = normalized enrichment score; padj = adjusted p-value. e, Pie-charts, showing the distribution of insulin-concordant/discordant MZ cotwin pairs, from the Danish twin cohort, in either low- (blue chart), or high-NNAT expressing couples (yellow chart). The definition of insulin-concordant/discordant couples was obtained by Gaussian finite mixture modeling (see Methods section). f, Box- and violin-plots of BMI discordance distributions, represented as inter co-twin differences in the Danish twin cohort. Solid horizontal lines and black points represent means and medians in the box-plots, respectively. * p-value = 0.03, as assessed by the Bartlett’s test of homogeneity of variances. Blue and yellow triangles represent co-twin pairs expressing averaged low and high NNAT levels, respectively. In box-plots, the lower and upper hinges = 25th and 75th percentiles. The upper/lower whiskers = largest/smallest observation less/greater than upper/lower hinge + 1.5 * IQR. Central median = 50% quantile.
