Abstract
The analysis of complex diseases was revolutionized by the ability to genotype at a genome-wide level tagging common SNPs in sufficiently large, and therefore adequately powered, population sample sets. This technological breakthrough has led to thousands of genetic variants being robustly associated with a multitude of phenotypic traits. These findings have illuminated novel genes and previously unknown pathways in the pathogenesis of disease, although in the majority of loci the functional mechanism remains unknown. The integration of this genomic information with epigenomic and transcriptomic data from these regions is one of the next steps in unraveling their biological significance. Allele-specific methylation influences allele-specific expression; therefore, the methylation state of the haplotypes within genetically associated regions can determine epigenetic differences with potential functional effects. DNA methylation data and association-determined risk and nonrisk haplotypes can be compared by a haplotype-specific methylation analysis. These are the first forays into what will become an increasingly routine multidimensional analysis as whole-genome, epigenome and transcriptome sequencing data become easily obtainable, with existing second- and soon to be available third-generation sequencing analyzers. Concise understanding of the functional implications of these genome-wide association-derived risk factors, plus rare variants discovered from deep sequencing experiments currently underway, will enable personalized risk and prevention profiling, as well as treatment, to come to fruition.
Acknowledgements
The author would like to acknowledge the support of Professor Stephan Beck.
Financial & competing interests disclosure
Christopher Bell is funded by the Wellcome Trust (084071). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.