dc.contributor.author | Luijk, R | |
dc.contributor.author | Wu, H | |
dc.contributor.author | Ward-Caviness, CK | |
dc.contributor.author | Hannon, E | |
dc.contributor.author | Carnero-Montoro, E | |
dc.contributor.author | Min, JL | |
dc.contributor.author | Mandaviya, P | |
dc.contributor.author | Müller-Nurasyid, M | |
dc.contributor.author | Mei, H | |
dc.contributor.author | van der Maarel, SM | |
dc.contributor.author | Beekman, M | |
dc.contributor.author | der Breggen, RV | |
dc.contributor.author | Deelen, J | |
dc.contributor.author | Lakenberg, N | |
dc.contributor.author | Moed, M | |
dc.contributor.author | Suchiman, HED | |
dc.contributor.author | Arindrarto, W | |
dc.contributor.author | van’t Hof, P | |
dc.contributor.author | Jan Bonder, M | |
dc.contributor.author | Deelen, P | |
dc.contributor.author | Tigchelaar, EF | |
dc.contributor.author | Zhernakova, A | |
dc.contributor.author | Zhernakova, DV | |
dc.contributor.author | van Dongen, J | |
dc.contributor.author | Hottenga, JJ | |
dc.contributor.author | Pool, R | |
dc.contributor.author | Isaacs, A | |
dc.contributor.author | Hofman, BA | |
dc.contributor.author | Jhamai, M | |
dc.contributor.author | van der Kallen, CJH | |
dc.contributor.author | Schalkwijk, CG | |
dc.contributor.author | Stehouwer, CDA | |
dc.contributor.author | van den Berg, LH | |
dc.contributor.author | van Galen, M | |
dc.contributor.author | Vermaat, M | |
dc.contributor.author | van Rooij, J | |
dc.contributor.author | Uitterlinden, AG | |
dc.contributor.author | Verbiest, M | |
dc.contributor.author | Verkerk, M | |
dc.contributor.author | Kielbasa, PSM | |
dc.contributor.author | Bot, J | |
dc.contributor.author | Nooren, I | |
dc.contributor.author | van Dijk, F | |
dc.contributor.author | Swertz, MA | |
dc.contributor.author | van Heemst, D | |
dc.contributor.author | Relton, C | |
dc.contributor.author | Mill, J | |
dc.contributor.author | Waldenberger, M | |
dc.contributor.author | Bell, JT | |
dc.contributor.author | Jansen, R | |
dc.contributor.author | Zhernakova, A | |
dc.contributor.author | Franke, L | |
dc.contributor.author | ‘t Hoen, PAC | |
dc.contributor.author | Boomsma, DI | |
dc.contributor.author | van Duijn, CM | |
dc.contributor.author | van Greevenbroek, MMJ | |
dc.contributor.author | Veldink, JH | |
dc.contributor.author | Wijmenga, C | |
dc.contributor.author | van Meurs, J | |
dc.contributor.author | Daxinger, L | |
dc.contributor.author | Slagboom, PE | |
dc.contributor.author | van Zwet, EW | |
dc.contributor.author | Heijmans, BT | |
dc.contributor.author | BIOS Consortium | |
dc.date.accessioned | 2018-09-18T12:26:58Z | |
dc.date.issued | 2018-09-14 | |
dc.description.abstract | X-chromosome inactivation (XCI), i.e., the inactivation of one of the female X chromosomes, restores equal expression of X-chromosomal genes between females and males. However, ~10% of genes show variable degrees of escape from XCI between females, although little is known about the causes of variable XCI. Using a discovery data-set of 1867 females and 1398 males and a replication sample of 3351 females, we show that genetic variation at three autosomal loci is associated with female-specific changes in X-chromosome methylation. Through cis-eQTL expression analysis, we map these loci to the genes SMCHD1/METTL4, TRIM6/HBG2, and ZSCAN9. Low-expression alleles of the loci are predominantly associated with mild hypomethylation of CpG islands near genes known to variably escape XCI, implicating the autosomal genes in variable XCI. Together, these results suggest a genetic basis for variable escape from XCI and highlight the potential of a population genomics approach to identify genes involved in XCI. | en_GB |
dc.description.sponsorship | This research was financially supported by several institutions: BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO, numbers 184.021.007 and 184.033.111); the UK Medical Research Council; Wellcome (www.wellcome.ac.uk; [grant number 102215/2/13/2 to ALSPAC]); the University of Bristol to ALSPAC; the UK Economic and Social Research Council (www.esrc.ac.uk; [ES/N000498/1] to CR); the UK Medical Research Council (www.mrc.ac.uk; grant numbers [MC_UU_12013/1, MC_UU_12013/2 to JLM, CR]); the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria; the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ; the Wellcome Trust, Medical Research Council, European Union (EU), and the National Institute for Health Research (NIHR)- funded BioResource, Clinical Research Facility, and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. | en_GB |
dc.identifier.citation | Vol. 9, article 3738 | en_GB |
dc.identifier.doi | 10.1038/s41467-018-05714-3 | |
dc.identifier.uri | http://hdl.handle.net/10871/34025 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer Nature | en_GB |
dc.rights | © The Author(s) 2018. 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. | en_GB |
dc.title | Autosomal genetic variation is associated with DNA methylation in regions variably escaping X-chromosome inactivation | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2018-09-18T12:26:58Z | |
dc.identifier.issn | 2041-1723 | |
dc.description | This is the final version of the article. Available from Springer Nature via the DOI in this record. | en_GB |
dc.description | Raw data were submitted to the European Genome-phenome Archive (EGA) under accession EGAS00001001077. | en_GB |
dc.identifier.journal | Nature Communications | en_GB |