Differential methylation of the TRPA1 promoter in pain sensitivity View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-12

AUTHORS

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, The MuTHER Consortium, Kourosh R. Ahmadi, Chrysanthi Ainali, Amy Barrett, Veronique Bataille, Jordana T. Bell, Alfonso Buil, Panos Deloukas, Emmanoil T. Dermitzakis, Antigone S. Dimas, Richard Durbin, Daniel Glass, Elin Grundberg, Neelam Hassanali, Asa K. Hedman, Catherine Ingle, David Knowles, Maria Krestyaninova, Cecilia M. Lindgren, Christopher E. Lowe, Mark I. McCarthy, Eshwar Meduri, Paola di Meglio, Josine L. Min, Stephen B. Montgomery, Frank O. Nestle, Alexandra C. Nica, James Nisbet, Stephen O’Rahilly, Leopold Parts, Simon Potter, Magdalena Sekowska, So-Youn Shin, Kerrin S. Small, Nicole Soranzo, Tim D. Spector, Gabriela Surdulescu, Mary E. Travers, Loukia Tsaprouni, Sophia Tsoka, Alicja Wilk, Tsun-Po Yang, Krina T. Zondervan, F.M.K. Williams, N. Li, P. Deloukas, S. Beck, S.B. McMahon, J. Wang, S.L. John, T.D. Spector

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. More... »

PAGES

2978

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncomms3978

DOI

http://dx.doi.org/10.1038/ncomms3978

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1021358038

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24496475


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