Genome-epigenome interactions associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

被引:27
作者
Herrera, Santiago [1 ,2 ,7 ]
de Vega, Wilfred C. [1 ,2 ,3 ]
Ashbrook, David [1 ,2 ,8 ]
Vernon, Suzanne D. [4 ,9 ]
McGowan, Patrick O. [1 ,2 ,3 ,5 ,6 ]
机构
[1] Univ Toronto, Ctr Environm Epigenet & Dev, Scarborough, ON, Canada
[2] Univ Toronto, Dept Biol Sci, Scarborough, ON, Canada
[3] Univ Toronto, Dept Cell & Syst Biol, Toronto, ON, Canada
[4] Solve ME CFS Initiat, Los Angeles, CA USA
[5] Univ Toronto, Dept Psychol, Toronto, ON, Canada
[6] Univ Toronto, Fac Med, Dept Physiol, Toronto, ON, Canada
[7] Lehigh Univ, Dept Biol Sci, Bethlehem, PA 18015 USA
[8] Univ Tennessee, Ctr Hlth Sci, Dept Genet Genom & Informat, Memphis, TN 38163 USA
[9] Bateman Horne Ctr Excellence, Salt Lake City, UT USA
关键词
DNA methylation; genotype; Chronic Fatigue Syndrome; Myalgic Encephalomyelitis; mQTL; DNA METHYLATION; NITROSATIVE STRESS; WIDE ASSOCIATION; PREVALENCE; POPULATION; CELLS; CHOLECYSTOKININ; IMMUNE; RECEPTORS; PATHWAYS;
D O I
10.1080/15592294.2018.1549769
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex disease of unknown etiology. Multiple studies point to disruptions in immune functioning in ME/CFS patients as well as specific genetic polymorphisms and alterations of the DNA methylome in lymphocytes. However, potential interactions between DNA methylation and genetic background in relation to ME/CFS have not been examined. In this study we explored this association by characterizing the epigenetic (similar to 480 thousand CpG loci) and genetic (similar to 4.3 million SNPs) variation between cohorts of ME/CFS patients and healthy controls. We found significant associations of DNA methylation states in T-lymphocytes at several CpG loci and regions with ME/CFS phenotype. These methylation anomalies are in close proximity to genes involved with immune function and cellular metabolism. Finally, we found significant correlations of genotypes with methylation modifications associated with ME/CFS. The findings from this study highlight the role of epigenetic and genetic interactions in complex diseases, and suggest several genetic and epigenetic elements potentially involved in the mechanisms of disease in ME/CFS.
引用
收藏
页码:1174 / 1190
页数:17
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