DNA methylation in peripheral tissues and left-handedness

Veronika V. Odintsova; Matthew Suderman; Fiona A. Hagenbeek; Doretta Caramaschi; Jouke Jan Hottenga; René Pool; Conor V. Dolan; Lannie Ligthart; Catharina E.M. van Beijsterveldt; Gonneke Willemsen; Eco J.C. de Geus; Jeffrey J. Beck; Erik A. Ehli; Gabriel Cuellar-Partida; David M. Evans; Sarah E. Medland; Caroline L. Relton; Dorret I. Boomsma; Jenny van Dongen; Bastiaan T. Heijmans; Peter A.C. ’t Hoen; Joyce van Meurs; Aaron Isaacs; Rick Jansen; Lude Franke; Dorret I. Boomsma; René Pool; Jenny van Dongen; Jouke J. Hottenga; Marleen M.J. van Greevenbroek; Coen D.A. Stehouwer; Carla J.H. van der 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; Joyce van Meurs; P. Mila Jhamai; Michael Verbiest; BIOS Consortium; Cohort collection; Data Analysis Group; Data Generation; Data management and computational infrastructure; Management Team

doi:10.1038/s41598-022-08998-0

DNA methylation in peripheral tissues and left-handedness

Veronika V. Odintsova^*, Matthew Suderman, Fiona A. Hagenbeek, Doretta Caramaschi, Jouke Jan Hottenga, René Pool, Conor V. Dolan, Lannie Ligthart, Catharina E.M. van Beijsterveldt, Gonneke Willemsen, Eco J.C. de Geus, Jeffrey J. Beck, Erik A. Ehli, Gabriel Cuellar-Partida, David M. Evans, Sarah E. Medland, Caroline L. Relton, Dorret I. Boomsma, Jenny van Dongen^*, Bastiaan T. HeijmansPeter A.C. ’t Hoen, Joyce van Meurs, Aaron Isaacs, Rick Jansen, Lude Franke, Dorret I. Boomsma, René Pool, Jenny van Dongen^*, Jouke J. Hottenga, Marleen M.J. van Greevenbroek, Coen D.A. Stehouwer, Carla J.H. van der 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, Joyce van Meurs, P. Mila Jhamai, Michael Verbiest, BIOS Consortium, Cohort collection, Data Analysis Group, Data Generation, Data management and computational infrastructure, Management Team

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Article number	5606
Number of pages	16
Journal	Scientific Reports
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41598-022-08998-0
Publication status	Published - 1 Dec 2022

Access to Document

10.1038/s41598-022-08998-0Licence: CC BY

Cite this

Odintsova, V. V., Suderman, M., Hagenbeek, F. A., Caramaschi, D., Hottenga, J. J., Pool, R., Dolan, C. V., Ligthart, L., van Beijsterveldt, C. E. M., Willemsen, G., de Geus, E. J. C., Beck, J. J., Ehli, E. A., Cuellar-Partida, G., Evans, D. M., Medland, S. E., Relton, C. L., Boomsma, D. I., van Dongen, J., ... Management Team (2022). DNA methylation in peripheral tissues and left-handedness. Scientific Reports, 12(1), Article 5606. https://doi.org/10.1038/s41598-022-08998-0

@article{265702011d5d4eedbf458f3d4d081c6f,

title = "DNA methylation in peripheral tissues and left-handedness",

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.",

author = "Odintsova, {Veronika V.} and Matthew Suderman and Hagenbeek, {Fiona A.} and Doretta Caramaschi and Hottenga, {Jouke Jan} and Ren{\'e} Pool and Dolan, {Conor V.} and Lannie Ligthart and {van Beijsterveldt}, {Catharina E.M.} and Gonneke Willemsen and {de Geus}, {Eco J.C.} and Beck, {Jeffrey J.} and Ehli, {Erik A.} and Gabriel Cuellar-Partida and Evans, {David M.} and Medland, {Sarah E.} and Relton, {Caroline L.} and Boomsma, {Dorret I.} and {van Dongen}, Jenny and Heijmans, {Bastiaan T.} and {{\textquoteright}t Hoen}, {Peter A.C.} and {van Meurs}, Joyce and Aaron Isaacs and Rick Jansen and Lude Franke and Boomsma, {Dorret I.} and Ren{\'e} Pool and {van Dongen}, Jenny and Hottenga, {Jouke J.} and {van Greevenbroek}, {Marleen M.J.} and Stehouwer, {Coen D.A.} and {van der Kallen}, {Carla J.H.} and Schalkwijk, {Casper G.} and Cisca Wijmenga and Lude Franke and Sasha Zhernakova and Tigchelaar, {Ettje F.} and Slagboom, {P. Eline} and Marian Beekman and Joris Deelen and {van Heemst}, Diana and Veldink, {Jan H.} and {Van den Berg}, {Leonard H.} and {van Duijn}, {Cornelia M.} and Hofman, {Bert A.} and Aaron Isaacs and Uitterlinden, {Andr{\'e} G.} and {van Meurs}, Joyce and Jhamai, {P. Mila} and Michael Verbiest and {BIOS Consortium} and {Cohort collection} and {Data Analysis Group} and {Data Generation} and {Data management and computational infrastructure} and {Management Team}",

note = "Funding Information: GRANT SUPPORT: Amsterdam Public Health Institute Methodology travel grant VVO; KNAW Academy Professor Award (PAH/6635) to DIB. JvD is supported by NWO Large Scale infrastructures, X-omics (184.034.019). The UK Medical Research Council and Wellcome (Grant Ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grantacknowledgements.pdf). This research was specifically funded by the BBSRC (grant numbers BBI025751/1 and BB/I025263/1). M.S., C.R. and D.C. are funded by the MRC (Grant Numbers MC_UU_00011/5 and MC_UU_00011/1). GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. The NTR received funding from the Netherlands Organization for Scientific Research (NWO): Biobanking and Biomolecular Research Infrastructure (BBMRI\u2013NL, 184.021.007; 184.033.111) and Netherlands Twin Registry Repository NWO 480-15-001/674. This work was also supported by \u201CAggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies\u201D project (ACTION). ACTION received funding from the European Union Seventh Framework Program (FP7/2007-2013) under Grant Agreement No. 602768. SEM is supported by NHMRC Investigator Grant APP1172917. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript we are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole NTR and ALSPAC teams, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. Publisher Copyright: {\textcopyright} The Author(s) 2022.",

year = "2022",

month = dec,

day = "1",

doi = "10.1038/s41598-022-08998-0",

language = "English",

volume = "12",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

Odintsova, VV, Suderman, M, Hagenbeek, FA, Caramaschi, D, Hottenga, JJ, Pool, R, Dolan, CV, Ligthart, L, van Beijsterveldt, CEM, Willemsen, G, de Geus, EJC, Beck, JJ, Ehli, EA, Cuellar-Partida, G, Evans, DM, Medland, SE, Relton, CL, Boomsma, DI, van Dongen, J, Heijmans, BT, ’t Hoen, PAC, van Meurs, J, Isaacs, A, Jansen, R, Franke, L, Boomsma, DI, Pool, R, van Dongen, J, Hottenga, JJ, van Greevenbroek, MMJ, Stehouwer, CDA, van der Kallen, CJH , Schalkwijk, CG, Wijmenga, C, Franke, L, Zhernakova, S, Tigchelaar, EF, Slagboom, PE, Beekman, M, Deelen, J, van Heemst, D, Veldink, JH, Van den Berg, LH, van Duijn, CM, Hofman, BA, Isaacs, A, Uitterlinden, AG, van Meurs, J, Jhamai, PM, Verbiest, M, BIOS Consortium, Cohort collection, Data Analysis Group, Data Generation, Data management and computational infrastructure & Management Team 2022, 'DNA methylation in peripheral tissues and left-handedness', Scientific Reports, vol. 12, no. 1, 5606. https://doi.org/10.1038/s41598-022-08998-0

TY - JOUR

T1 - DNA methylation in peripheral tissues and left-handedness

AU - Odintsova, Veronika V.

AU - Suderman, Matthew

AU - Hagenbeek, Fiona A.

AU - Caramaschi, Doretta

AU - Hottenga, Jouke Jan

AU - Pool, René

AU - Dolan, Conor V.

AU - Ligthart, Lannie

AU - van Beijsterveldt, Catharina E.M.

AU - Willemsen, Gonneke

AU - de Geus, Eco J.C.

AU - Beck, Jeffrey J.

AU - Ehli, Erik A.

AU - Cuellar-Partida, Gabriel

AU - Evans, David M.

AU - Medland, Sarah E.

AU - Relton, Caroline L.

AU - Boomsma, Dorret I.

AU - van Dongen, Jenny

AU - Heijmans, Bastiaan T.

AU - ’t Hoen, Peter A.C.

AU - van Meurs, Joyce

AU - Isaacs, Aaron

AU - Jansen, Rick

AU - Franke, Lude

AU - Boomsma, Dorret I.

AU - Pool, René

AU - van Dongen, Jenny

AU - Hottenga, Jouke J.

AU - van Greevenbroek, Marleen M.J.

AU - Stehouwer, Coen D.A.

AU - van der Kallen, Carla J.H.

AU - Schalkwijk, Casper G.

AU - Wijmenga, Cisca

AU - Franke, Lude

AU - Zhernakova, Sasha

AU - Tigchelaar, Ettje F.

AU - Slagboom, P. Eline

AU - Beekman, Marian

AU - Deelen, Joris

AU - van Heemst, Diana

AU - Veldink, Jan H.

AU - Van den Berg, Leonard H.

AU - van Duijn, Cornelia M.

AU - Hofman, Bert A.

AU - Isaacs, Aaron

AU - Uitterlinden, André G.

AU - van Meurs, Joyce

AU - Jhamai, P. Mila

AU - Verbiest, Michael

AU - BIOS Consortium

AU - Cohort collection

AU - Data Analysis Group

AU - Data Generation

AU - Data management and computational infrastructure

AU - Management Team

N1 - Funding Information: GRANT SUPPORT: Amsterdam Public Health Institute Methodology travel grant VVO; KNAW Academy Professor Award (PAH/6635) to DIB. JvD is supported by NWO Large Scale infrastructures, X-omics (184.034.019). The UK Medical Research Council and Wellcome (Grant Ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grants funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grantacknowledgements.pdf). This research was specifically funded by the BBSRC (grant numbers BBI025751/1 and BB/I025263/1). M.S., C.R. and D.C. are funded by the MRC (Grant Numbers MC_UU_00011/5 and MC_UU_00011/1). GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. The NTR received funding from the Netherlands Organization for Scientific Research (NWO): Biobanking and Biomolecular Research Infrastructure (BBMRI\u2013NL, 184.021.007; 184.033.111) and Netherlands Twin Registry Repository NWO 480-15-001/674. This work was also supported by \u201CAggression in Children: Unraveling gene-environment interplay to inform Treatment and InterventiON strategies\u201D project (ACTION). ACTION received funding from the European Union Seventh Framework Program (FP7/2007-2013) under Grant Agreement No. 602768. SEM is supported by NHMRC Investigator Grant APP1172917. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript we are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole NTR and ALSPAC teams, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. Publisher Copyright: © The Author(s) 2022.

PY - 2022/12/1

Y1 - 2022/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-022-08998-0

DO - 10.1038/s41598-022-08998-0

M3 - Article

SN - 2045-2322

VL - 12

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 5606

ER -

DNA methylation in peripheral tissues and left-handedness

Abstract

Access to Document

Fingerprint

Cite this