RT Journal Article
T1 Autosomal genetic variation is associated with DNA methylation in regions variably escaping X-chromosome inactivation.
A1 Luijk, René
A1 Wu, Haoyu
A1 Ward-Caviness, Cavin K
A1 Hannon, Eilis
A1 Carnero-Montoro, Elena
A1 Min, Josine L
A1 Mandaviya, Pooja
A1 Müller-Nurasyid, Martina
A1 Mei, Hailiang
A1 van der Maarel, Silvere M
A1 BIOS Consortium, 
A1 Relton, Caroline
A1 Mill, Jonathan
A1 Waldenberger, Melanie
A1 Bell, Jordana T
A1 Jansen, Rick
A1 Zhernakova, Alexandra
A1 Franke, Lude
A1 't Hoen, Peter A C
A1 Boomsma, Dorret I
A1 van Duijn, Cornelia M
A1 van Greevenbroek, Marleen M J
A1 Veldink, Jan H
A1 Wijmenga, Cisca
A1 van Meurs, Joyce
A1 Daxinger, Lucia
A1 Slagboom, P Eline
A1 van Zwet, Erik W
A1 Heijmans, Bastiaan T
AB 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.
YR 2018
FD 2018-09-14
LK http://hdl.handle.net/10668/12949
UL http://hdl.handle.net/10668/12949
LA en
DS RISalud
RD Apr 11, 2025