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. 2022 Apr 4;12:5606. doi: 10.1038/s41598-022-08998-0

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Flowchart of epigenome-wide association study of left-handedness. The flowchart summarizes the study design. The primary analyses included EWASs in NTR adults and ALSPAC adults, followed by meta-analysis to identify DNA methylation sites associated with left-handedness. The secondary analyses included: (1) left-handedness GWAS loci follow-up; (2) longitudinal analysis of DNA methylation at four ages in ALSPAC offspring; (3) analysis of buccal cell DNA methylation in NTR children; (4) analysis of DNA methylation differences between left and right-handed co-twins from NTR discordant MZ twin pairs and (5) polygenic and DNA methylation scores prediction. For left-handedness prediction, polygenic scores (PGS) were created based on left-handedness GWAS summary statistics not including NTR/ALSPAC. Methylation scores (MS) were created based on weights from EWASs in NTR adults, ALSPAC adults, NTR children and ALSPAC offspring at 7 years old to estimate the predictive performance. LH, left-handed; RH, right-handed. DMR, differentially methylated region. EWAS, epigenome-wide association study. GWAS, genome-wide association study. GoDMC, Genetics of DNA Methylation Consortium. mQTL, methylation quantitative trait locus. Blood, buccal cells indicate tissue of DNA methylation. 450 k, EPIC indicate the platform for DNA methylation measurement.