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Differential methylation of the TRPA1 promoter in pain sensitivity

Bell, JT and Loomis, AK and Butcher, LM and Gao, F and Zhang, B and Hyde, CL and Sun, J and Wu, H and Ward, K and Harris, J and Scollen, S and Davies, MN and Schalkwyk, LC and Mill, J and Williams, FMK and Li, N and Deloukas, P and Beck, S and McMahon, SB and Wang, J and John, SL and Spector, TD (2014) 'Differential methylation of the TRPA1 promoter in pain sensitivity.' Nature Communications, 5 (1). 2978-. ISSN 2041-1723

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Chronic pain is a global public health problem, but the underlying molecular mechanisms are not fully understood. Here we examine genome-wide DNA methylation, first in 50 identical twins discordant for heat pain sensitivity and then in 50 further unrelated individuals. Whole-blood DNA methylation was characterized at 5.2 million loci by MeDIP sequencing and assessed longitudinally to identify differentially methylated regions associated with high or low pain sensitivity (pain DMRs). Nine meta-analysis pain DMRs show robust evidence for association (false discovery rate 5) with the strongest signal in the pain gene TRPA1 (P=1.2 �? 10(-13)). Several pain DMRs show longitudinal stability consistent with susceptibility effects, have similar methylation levels in the brain and altered expression in the skin. Our approach identifies epigenetic changes in both novel and established candidate genes that provide molecular insights into pain and may generalize to other complex traits.

Item Type: Article
Uncontrolled Keywords: MuTHER Consortium; Humans; Hyperalgesia; Calcium Channels; Nerve Tissue Proteins; Case-Control Studies; DNA Methylation; Gene Expression; Epigenesis, Genetic; Twins, Monozygotic; Aged; Aged, 80 and over; Middle Aged; Female; Male; Transient Receptor Potential Channels; Promoter Regions, Genetic; Genome-Wide Association Study; TRPA1 Cation Channel
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 23 Oct 2014 15:23
Last Modified: 15 Jan 2022 00:41

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