Fig. 3: Metabolic heterogeneity was responsible for the high rate of misclassification within the standard BMI classes.
a, Difference of the omics-inferred BMI from the measured BMI (ΔBMI). Padj: adjusted P value of two-sided Pearson’s correlation test with the Benjamini–Hochberg method across the six combinations (n, number of participants in each BMI class; total n = 1,277 participants). The line in the histogram panel indicates the kernel density estimate. b, Difference in ΔBMI between clinically defined metabolic health conditions within the normal or obese BMI class. Each comparison value indicates adjusted P value, calculated from OLS linear regression with BMI, sex, age and ancestry principal components as covariates while adjusting multiple testing with the Benjamini–Hochberg method across the eight (2 BMI classes × 4 omics categories) regressions. c, Misclassification rate of overall cohort or each BMI class against the omics-inferred BMI class. Reference range: the previously reported misclassification rate36,37. The underweight BMI class is not presented owing to small sample size, but its misclassification rate was 80% against CombiBMI class and 100% against the others. d,e, Difference in the obesity-related clinical blood marker (d) or BMI-associated physiological feature (e) between the matched and mismatched groups within the normal or obese BMI class. Each comparison value indicates adjusted P value, calculated from OLS linear regression with BMI, sex, age and ancestry principal components as covariates while adjusting multiple testing with the Benjamini–Hochberg method across the 40 (d, 2 BMI classes × 2 omics categories × 10 markers) or 216 (e, 2 BMI classes × 4 omics categories × 27 features) regressions. Four of the 27 features that were significantly associated with BMI (Fig. 1c) are representatively presented in e, and the other results are found in Supplementary Data 6. 25(OH)D, 25-hydroxyvitamin D; a.u., arbitrary units. b,d,e, Data: the standard box plot (Methods); n = 373 (b, Healthy in Normal), 49 (b, Unhealthy in Normal), 208 (b, Healthy in Obese) or 241 (b, Unhealthy in Obese) participants (see Supplementary Data 6 for each sample size in d and e). All exact values of test summaries are found in Supplementary Data 6 and 10.
