DNA methylation in peripheral tissues and left-handedness
Veronika V. Odintsova, Matthew Suderman, Fiona A. Hagenbeek, Doretta Caramaschi, Jouke‐Jan Hottenga, René Pool, Management Team, Bastiaan T. Heijmans, Peter A.C. ’t Hoen, Joyce van Meurs, Aaron Isaacs, Rick Jansen, Lude Franke, Cohort collection, Dorret I. Boomsma, René Pool, Jenny van Dongen, Jouke‐Jan Hottenga, Marleen M. J. van Greevenbroek, Coen D.A. Stehouwer, Carla Kallen, Casper G. Schalkwijk, Cisca Wijmenga, Lude Franke, Sasha Zhernakova, Ettje F. Tigchelaar, P. Eline Slagboom, Marian Beekman, Joris Deelen, Diana van Heemst, Jan H. Veldink, Leonard H. van den Berg, Cornelia M. van Duijn, Bert A. Hofman, Aaron Isaacs, André G. Uitterlinden, Data Generation, Joyce van Meurs, P. Mila Jhamai, Michaël Verbiest, H. Eka D. Suchiman, Marijn Verkerk, Ruud van der Breggen, Jeroen van Rooij, Nico Lakenberg, Data management and computational infrastructure, Hailiang Mei, Maarten van Iterson, Michiel van Galen, Jan Bot, Dasha V. Zhernakova, Rick Jansen, Peter van ‘t Hof, Patrick Deelen, Irene Nooren, Peter A.C. ’t Hoen, Bastiaan T. Heijmans, Matthijs Moed, Data Analysis Group, Lude Franke, Martijn Vermaat, Dasha V. Zhernakova, René Luijk, Marc Jan Bonder, Maarten van Iterson, Patrick Deelen, Freerk van Dijk, Michiel van Galen, Wibowo Arindrarto, Szymon M. Kiełbasa, Morris A. Swertz, Erik W. van Zwet, Rick Jansen, Peter A.C. ’t Hoen, Bastiaan T. Heijmans, Conor V. Dolan, Lannie Ligthart, Catharina E. M. van Beijsterveldt, Gonneke Willemsen, Eco J. C. de Geus, Jeffrey J. Beck, Erik A. Ehli, Gabriel Cuéllar-Partida, David M. Evans, Sarah E. Medland, Caroline L. Relton, Dorret I. Boomsma, Jenny van Dongen
Abstract
Handedness has low heritability and epigenetic mechanisms have been proposed as an etiological mechanism. To examine this hypothesis, we performed an epigenome-wide association study of left-handedness. In a meta-analysis of 3914 adults of whole-blood DNA methylation, we observed that CpG sites located in proximity of handedness-associated genetic variants were more strongly associated with left-handedness than other CpG sites (P = 0.04), but did not identify any differentially methylated positions. In longitudinal analyses of DNA methylation in peripheral blood and buccal cells from children (N = 1737), we observed moderately stable associations across age (correlation range [0.355-0.578]), but inconsistent across tissues (correlation range [- 0.384 to 0.318]). We conclude that DNA methylation in peripheral tissues captures little of the variance in handedness. Future investigations should consider other more targeted sources of tissue, such as the brain.