期刊
EPIGENOMICS
卷 13, 期 8, 页码 613-630出版社
FUTURE MEDICINE LTD
DOI: 10.2217/epi-2020-0424
关键词
CPSP; DNA methylation; epigenetics; genetics; mechanisms; meQTL; methylation quantitative trait; PARK16; postoperative pain
资金
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [5K23HD082782]
- Center for Pediatric Genomics, Shared Facility Discovery Award, from Cincinnati Children's Hospital Medical Center
- National Institute of Arthtritis and Muscoskeletal and Skin Diseases [1R01AR075857-01]
- NIH [R01AI141569-01]
- NIH/NIEHS [P30ES023513]
The study identified differences in pain measures between CPSP patients and non-patients, with CPSP risk meQTLs being associated with DNA methylation, indicating a genetic risk. These results suggest that epigenetic mechanisms may mediate the occurrence of CPSP.
Background: Overlap of pathways enriched by single nucleotide polymorphisms and DNA-methylation underlying chronic postsurgical pain (CPSP), prompted pilot study of CPSP-associated methylation quantitative trait loci (meQTL). Materials & methods: Children undergoing spine-fusion were recruited prospectively. Logistic-regression for genome- and epigenome-wide CPSP association and DNA-methylation-single nucleotide polymorphism association/mediation analyses to identify meQTLs were followed by functional genomics analyses. Results: CPSP (n = 20/58) and non-CPSP groups differed in pain-measures. Of 2753 meQTLs, DNA-methylation at 127 cytosine-guanine dinucleotides mediated association of 470 meQTLs with CPSP (p < 0.05). At PARK16 locus, CPSP risk meQTLs were associated with decreased DNA-methylation at RAB7L1 and increased DNA-methylation at PM20D1. Corresponding RAB7L1/PM20D1 blood eQTLs (GTEx) and cytosine-guanine dinucleotide-loci enrichment for histone marks, transcription factor binding sites and ATAC-seq peaks suggest altered transcription factor-binding. Conclusion: CPSP-associated meQTLs indicate epigenetic mechanisms mediate genetic risk.
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