Examination of the AoU database reveals an association between elevated serum B₁₂ levels and the prevalence of CH. In the AoU genomic database, 1256 individuals were positive for CH and had serum B₁₂ information available. They were compared to 18 174 individuals without CH for whom B₁₂ serum concentrations were also available. B₁₂ levels were categorized into the following bins (pg/mL): 0 to 200, 201 to 400, 401 to 600. 601-800, 801-1000, and >1000 and used to determine CH prevalence (A) and OR (B), calculated by Fisher exact test, with significant adjusted P value obtained by pairwise Fisher exact test for comparisons made between normal B₁₂ levels (200-800 pg/mL) vs above the normal levels (>1000 pg/mL), including 201 to 400 vs >1000 (OR, 1.37; P = .00525), 401 to 600 vs >1000 (OR, 1.45; P = .000545), and 601 to 800 vs >1000 (OR, 1.37; P = .009150) pg/mL (shown in red). (C) Median serum B₁₂ concentrations in individuals with CH, MDS, and AML compared to nonmutant individuals (no mutation; median with upper and lower quartiles are shown, significance calculated by Wilcoxon test). (D) Frequency and mutational spectrum of CH individuals in the AoU database. (E-F) Stratification by median serum B₁₂ concentration (pg/ml) per CH mutation (E) and comparison to other CH mutant or nonmutant individuals (median with upper and lower quartiles are shown, significance calculated by Wilcoxon test) (F). (G) Fold change in CH mutation frequency above vs below the median serum B₁₂ concentration of individuals with CH (P < .05 [by 2 proportional test]). AML, acute myeloid leukemia; MDS, myelodysplastic syndrome.