Comprehensive mechanistic characterization of mQTLs in an Asian population

Abstract Identification and characterization of methylation quantitative trait loci (mQTLs) can help elucidate the role of DNA methylation changes as a potential mediator of genetic risk loci. However, mQTLs remain poorly characterized: they have not yet been mapped in the largest ethnic populations, their cell-type specific nature has not been resolved, and the proportion of mQTLs attributed to different molecular mechanisms is unknown. Here we perform the first mQTL-mapping study in a large Han Chinese population, demonstrating that over 80% of mQTLs are shared with those identified in White Caucasians. We further estimate that over 90% of mQTLs are shared between different blood cell-lineages. mQTLs demonstrate a strong enrichment for variants influencing chromatin accessibility. We identify a number of GWAS-linked transcription factor trans-mQTL hotspots associated with eosinophilia, ulcerative colitis and body mass index, and a subset of trans-mQTLs within the NFKB-pathway that may mediate the risk of obesity. In summary, this study significantly expands our understanding of mQTLs and their potential role in mediating disease risk, whilst also contributing the first mQTL-database in an Asian population.