Differential methylation of the TRPA1 promoter in pain sensitivity
Davies, Matthew N.
Nature Publishing Group
Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/.
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.
Royal Society Wolfson Research Merit Award
EU-FP7 projects EPIGENESYS
European Research Council
This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.
Nature Communications, 2014, Vol. 5