Figure 2.
Variables Associated with BMI and Predicted BMI from the Metabolome
(A) Correlation between ridge regression model prediction of BMI and actual BMI for all unrelated individuals of European ancestry in the TwinsUK and Health Nucleus dataset. The identification of outliers is defined below: the pink box shows individuals with a much lower predicted BMI (mBMI) than actual BMI, and the yellow box shows individuals with a much higher mBMI than actual BMI.
(B) Factors associated with being an mBMI outlier. Participants were split into five groups: those whose metabolome accurately predicted their BMI (residual after accounting for age, sex, and BMI between −0.5 and 0.5) whose BMIs were either normal (18.5–25), overweight (25–30), or obese (>30), and those whose metabolome predicted a substantially higher mBMI than the actual BMI (residual < −0.5) or a substantially lower mBMI than the actual BMI (residual > 0.5). All y axis values are scaled to a range from 0 to 1 to allow comparison across groups.
(C) The same process is used to show DEXA imaging values associated with metabolic BMI outliers. The mBMI ≫ BMI and mBMI ≪ BMI groups had a comparable measured BMI and age; however, these two groups were statistically significantly different from each other (p < 0.01) for all modalities except blood pressure, LDL, total cholesterol, and polygenic risk score. Additionally, the mBMI ≫ BMI group was statistically significantly different from normal weight, metabolically healthy people (p < 0.01) for all traits (except LDL), while mBMI ≪ BMI individuals were only statistically different in diastolic blood pressure (p = 0.005). In contrast, outliers with mBMI ≪ BMI were always statistically significantly different from obese, metabolically obese individuals (except systolic blood pressure, LDL, and total cholesterol), while mBMI ≫ BMI individuals were only statistically different in percent body fat (p = 4.4 × 10−6). LDL, low-density lipoprotein; HDL, high-density lipoprotein. The correlations of each modality with mBMI can be found in Table S2.
Whiskers of boxplot extend to the most extreme points no greater than 1.5 times the interquartile range (distance between the first and third quartiles).