The current review has shown that knowledge of individual genetic variability and epigenetic regulation of gene expression underpins the understanding of nutritional regulation of optimal and sub-optimal brain health. Recent advances are providing insights into disorders ranging from cognitive impairment, depression and eating disorders to Alzheimer’s disease, schizophrenia and brain tumours. Future advances will involve very large-scale investigations of the whole genome and epigenomes of specific cell types, together with focused assessment of specific regulatory factors including protein-coding genes and non-coding RNAs (ncRNAs).
Considerable effort is now being made by large scale consortia to cope with the enormous sample sizes and vast amounts of data being generated by advances in genomics and epigenomics. The development of genome-wide association studies (GWAS) is enabling significant advances in identifying common disease-predisposing gene variants. However, the robust detection of disease-associated low-frequency alleles in complex diseases will require even larger study samples than those used in GWAS [36
]. Moreover, studies combining GWAS with a systems genetics approach will undoubtedly advance understanding of the complex pathways linking genetics, environment and disease [37
The International Human Epigenome Consortium (IHEC) incorporates inputs from scientists in North America, Europe, Australia, Japan and South Korea. Its primary goal is to provide free access to high-resolution reference human epigenome maps to the research community. A range of 21 normal and disease cell types are being investigated, including those from the fetal and adult nervous system. Epigenomic maps can be used to trace the origin of cells, dissect affected pathways and identify predictive biomarkers [46
]. The hope is that these maps will have an impact on the understanding, treatment and management of many diseases. Underpinning these advances is the need for a global biobanking strategy to harmonize the multiple interests of organizations, initiatives, resources and stakeholders, including patients [131
Technological advances cannot in themselves provide solutions to all problems associated with the aetiology and treatment of brain disorders. Future studies using innovative approaches and novel systems will also help to advance understanding of the links between nutrition and neuroscience. Some of these are highlighted in the present review. Evolutionary complexity is linked with increasingly large proportions of non-protein-coding sequences in the genome. Indeed, recent studies implicate ncRNAs in mediating changes in neural gene expression during evolution. They also suggest that the expansion of ncRNAs was in part responsible for the emergence of vertebrate complexity, especially in the brain, together with the increased cognitive and behavioural repertories of higher organisms [55
]. Comparative genomic and epigenomic studies in a wide range of species will therefore be of particular benefit in elucidating mechanisms underlying brain disorders [86
]. Key studies in development and neuroscience have been undertaken in many species including the fruit fly Drosophila melanogaster
, zebra fish, frog and mouse. Drosophila
has long been used as a model organism for studying diseases ranging from cancer to neurodegenerative disorders. Its versatile genetics and the ability to quickly generate multiple genetic variants could be of particular value in studying complex neuropsychiatric disorders such as autism and schizophrenia [134
]. Moreover, studies in a range of species is currently enabling significant progress in understanding the role of the Wnt/β-catenin cell signalling pathway in many neurological and neuropsychiatric disorders, including Alzheimer’s, schizophrenia and the devastating brain cancer glioma [133
In addition to the epigenetic studies in honeybees and locusts discussed in the current review, further novel approaches could, for example, involve molecular evolutionary studies of dietary selection. These should provide new insights into eating behaviours and disorders in humans. The giant panda Ailuropoda melanoleuca
has a highly specialized bamboo diet that is quite different from the carnivorous or omnivorous diets of other bears. Comprehensive sequence analysis of the genes involved in the appetite-reward system suggests a complex genetic background, possibly involving miRNAs and deficiencies in dopamine metabolism, behind the panda’s dietary switch [135
]. Progress in elucidating the complex role of nutrition in brain disorders will benefit considerably from future studies on ncRNAs. The predicted exponential rise in understanding of the role of ncRNAs in the central nervous system, combined with the versatility and relative simplicity of RNA chemistry, should make translation into diagnostic and therapeutic applications a reasonable possibility [56
It is probable that genomic and epigenomic technologies will continue to advance significantly, resulting in reduced costs and increased opportunities. This should enable large numbers of individual genomes and epigenomes to be analysed throughout the life-cycle in relation to multiple environmental variables including specific diets, nutrients, energy intake and physical activity. In the long-term, outcomes should include major benefits in relation to optimization of life-style and ameliorating any underlying genetic propensity for disease. However, major cautions and caveats must also be mentioned. Current concern with respect to the ethical use of personal data will only increase as the functions of millions of newly identified gene variants are elucidated. Moreover, it is essential that nutritionists and dietitians are involved at all stages of such investigations. Significant advances are now being made in relation to two highly relevant areas: the accurate assessment of dietary intake and life-style, and the education of professional nutritionists in the molecular and cellular basis of health and disease.
In summary, future advances in genomics and epigenomics will continue to provide new insights into the mechanisms that underpin the nutritional regulation of gene expression in the brain. Technological progress cannot in itself provide solutions to all biomedical problems. Innovative approaches combined with state-of-the-art techniques should suggest possibilities for preventing, ameliorating and treating the multiple complex brain disorders associated with adverse genetic and environmental factors.