New subtypes of allele-specific epigenetic effects: implications for brain development, function and disease

•Several different subtypes of epigenetic allelic effects exist in the brain.•Epigenetic allelic effects can be categorized according to heritability, clonality, and stability.•Epigenetic allelic effects are cell-type and developmental stage dependent.•Functional roles and effects on disease risk and progression are largely unexplored. Typically, it is assumed that the maternal and paternal alleles for most genes are equally expressed. Known exceptions include canonical imprinted genes, random X-chromosome inactivation, olfactory receptors and clustered protocadherins. Here, we highlight recent studies showing that allele-specific expression is frequent in the genome and involves subtypes of epigenetic allelic effects that differ in terms of heritability, clonality and stability over time. Different forms of epigenetic allele regulation could have different roles in brain development, function, and disease. An emerging area involves understanding allelic effects in a cell-type and developmental stage-specific manner and determining how these effects influence the impact of genetic variants and mutations on the brain. A deeper understanding of epigenetics at the allele and cellular level in the brain could help clarify the mechanisms underlying phenotypic variance.