Targeted Bisulfite Sequencing of Imprinting Control Regions in a 12-Individual Family Cohort: An Exploratory Pilot Linking Methylation Spatial Structure to Two Behavioral Dimensions

This exploratory pilot used targeted bisulfite sequencing to profile 16 imprinting control regions (ICRs) across 8 imprinted genes in 12 individuals from 4 families, testing whether ICR methylation carries molecular signals of two behavioral dimensions of innate predisposition. Personality traits are moderately heritable, yet their molecular carriers remain largely unknown. Within a dual-layer framework of innate predisposition and acquired personality, the author identified through long-term observation a set of highly reproducible non-Mendelian intergenerational transmission patterns, suggesting that innate predisposition may be linked to methylation at imprinting control regions. Using molecular features selected under the independently observed ABCD framework, the author found that the signals resided not in the average level of ICR methylation but in its internal spatial structure. The rationality dimension corresponded to methylation at specific KvDMR1 subregions (KCNQ1 difference r = +0.760), and the dominance dimension to the asymmetric methylation distribution within the PEG3 ICR (3′-half skewness r = +0.785). The two axes were nearly completely orthogonal at the epigenetic level (r = −0.038), and nearest-centroid classification matched behavioral labeling in 91.7% (11/12, full-sample resubstitution; exploratory finding).