Genetic influences on cortical myelination in the human brain

Cortical myelination, which is essential for interneuronal communication and neurodevelopment, has been reported to be under genetic control. However, the degree to which genes contribute to the variability of myelination, the pattern of genetic control, and how genes influence the organization of myelination are largely unknown. To answer these questions, the present study calculated heritability estimates for myelination of the cortical regions using the high quality structural magnetic resonance imaging (MRI) scans from the Human Connectome Project pedigree cohort (n = 873, 383/490 M/F, 22-36 years of age). Then, we used transcriptional profiles to evaluate the contribution of myelination-related genes (data from the Allen Human Brain Atlas) to explain interregional variations in cortical myelination. Our results showed that all the cortical areas were modestly to moderately influenced by genetic factors (h² = 29%-66%, all Ps < 0.05 after Bonferroni correction). The genetic control of cortical myelination showed bilateral symmetry and an anterior-to-posterior gradation. A bivariate model indicated that the regions are strongly genetically correlated with their homologs in the opposite cerebral hemisphere. A cross-modal analysis did not find a correlation between cortical myelination and the expression levels of myelination-related genes. This could have been due to the small number of samples with expression data in each cortical region. Overall, our findings suggest that cortical myelination is shaped by genetic factors and may be useful to bridge the underlying genetic variants and the cognitive functioning and related neuropsychiatric disorders.