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Differential methylation of the TRPA1 promoter in pain sensitivity

Authors :: Bell, J.T.
Loomis, A.K.
Butcher, L.M.
Gao, F.
Zhang, B.
Hyde, C.L.
Sun, J.
Wu, H.
Ward, K.
Harris, J.
Scollen, S.
Davies, M.N.
Schalkwyk, L.C.
Mill, J.
Ahmadi, Kourosh R.
Ainali, Chrysanthi
Barrett, Amy
Bataille, Veronique
Bell, Jordana T.
Buil, Alfonso
Deloukas, Panos
Dermitzakis, Emmanoil T.
Dimas, Antigone S.
Durbin, Richard
Glass, Daniel
Grundberg, Elin
Hassanali, Neelam
Hedman, Asa K.
Ingle, Catherine
Knowles, David
Krestyaninova, Maria
Lindgren, Cecilia M.
Lowe, Christopher E.
McCarthy, Mark I.
Meduri, Eshwar
di Meglio, Paola
Min, Josine L.
Montgomery, Stephen B.
Nestle, Frank O.
Nica, Alexandra C.
Nisbet, James
O’Rahilly, Stephen
Parts, Leopold
Potter, Simon
Sekowska, Magdalena
Shin, So-Youn
Small, Kerrin S.
Soranzo, Nicole
Spector, Tim D.
Surdulescu, Gabriela
Travers, Mary E.
Tsaprouni, Loukia
Tsoka, Sophia
Wilk, Alicja
Yang, Tsun-Po
Zondervan, Krina T.
Williams, F.M.K.
Li, N.
Deloukas, P.
Beck, S.
McMahon, S.B.
Wang, J.
John, S.L.
Spector, T.D.
Source :: Nature Communications; Vol 5, Nature Communications, Bell, J T, Loomis, A K, Butcher, L M, Gao, F, Zhang, B, Hyde, C L, Sun, J, Wu, H, Ward, K, Harris, J, Scollen, S, Davies, M N, Schalkwyk, L C, Mill, J, Williams, F M K, Li, N, Deloukas, P, Beck, S, McMahon, S B, Wang, J, John, S L, Spector, T D 2014, ' Differential methylation of the TRPA1 promoter in pain sensitivity ', Nature Communications, vol. 5, no. 1, 2978 . https://doi.org/10.1038/ncomms3978, Bell, J T, Loomis, A K, Butcher, L M, Gao, F, Zhang, B, Hyde, C L, Sun, J, Wu, H, Ward, K, Harris, J, Scollen, S, Davies, M N, Schalkwyk, L C, Mill, J, Williams, F M K, Li, N, Deloukas, P, Beck, S, McMahon, S B, Wang, J, John, S L & Spector, T D 2014, ' Differential methylation of the TRPA1 promoter in pain sensitivity ', Nature Communications, vol. 5, 2978 . https://doi.org/10.1038/ncomms3978
Publication Year :: 2014
Publisher :: NATURE PUBLISHING GROUP, 2014.
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.<br />Genetically identical twins provide a valuable resource to identify epigenetic factors associated with complex traits. Here the authors adopt this approach and find that differential methylation of the pain gene TRPA1 is associated with pain sensitivity in humans.