Reading and maths ability are shaped by an interaction of genetic and environmental factors. Roughly half of the behavioural variance that is measured when assessing reading and maths performance is explained by genetic variance, while the other half is explained by environmental variance (see Chapters 6 and 7). In this context, it is often overlooked that there is a large explanatory gap between what genes do and how behavioural performance is regulated. Genes do not act directly but indirectly on reading and maths ability, most notably by playing a role in the development of the brain, the biological information processing system that makes learning to read and do maths possible. More specifically, many candidate genes for dyslexia and dyscalculia encode protein structures in developing neural circuits that ultimately form the brain systems underlying reading and maths. This explanatory pathway involving genetic variation, brain systems for reading and maths, and learning difficulties in these two domains is the key topic of the present chapter.