Differential methylation of the TRPA1 promoter in pain sensitivity

J.T. Bell, A.K. Loomis, L.M. Butcher, F. Gao, B. Zhang, C.L. Hyde, J. Sun, H. Wu, K. Ward, J. Harris, S. Scollen, M.N. Davies, L.C. Schalkwyk, J. Mill, F.M.K. Williams, N. Li, P. Deloukas, S. Beck, S.B. McMahon, J. Wang (), S.L. John and T.D. Spector ()
Additional contact information
J.T. Bell: Kings College London
A.K. Loomis: Pfizer Research Laboratories
L.M. Butcher: Medical Genomics, UCL Cancer Institute, University College London
F. Gao: BGI-Shenzhen
B. Zhang: Pfizer Research Laboratories
C.L. Hyde: Pfizer Research Laboratories
J. Sun: BGI-Shenzhen
H. Wu: BGI-Shenzhen
K. Ward: Kings College London
J. Harris: Kings College London
S. Scollen: Pfizer Limited, Neusentis
M.N. Davies: Kings College London
L.C. Schalkwyk: Institute of Psychiatry, King’s College London
J. Mill: Institute of Psychiatry, King’s College London
F.M.K. Williams: Kings College London
N. Li: BGI-Shenzhen
P. Deloukas: William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London
S. Beck: Medical Genomics, UCL Cancer Institute, University College London
S.B. McMahon: Wolfson Centre for Age-Related Diseases, King’s College London
J. Wang: BGI-Shenzhen
S.L. John: Pfizer Research Laboratories
T.D. Spector: Kings College London

Nature Communications, 2014, vol. 5, issue 1, 1-11

Abstract: Abstract 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.

Date: 2014
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DOI: 10.1038/ncomms3978

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