Autosomal genetic variation is associated with DNA methylation in regions variably escaping X-chromosome inactivation

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 ge... Mehr ...

Verfasser: Luijk, René
Wu, Haoyu
Ward-Caviness, Cavin K.
Hannon, Eilis
Carnero-Montoro, Elena
Min, Josine L.
Mandaviya, Pooja
Müller-Nurasyid, Martina
Mei, Hailiang
van der Maarel, Silvere M.
Beekman, Marian
der Breggen, Ruud van
Deelen, Joris
Lakenberg, Nico
Moed, Matthijs
Suchiman, H. Eka D.
Arindrarto, Wibowo
van’t Hof, Peter
Jan Bonder, Marc
Deelen, Patrick
Tigchelaar, Ettje F.
Zhernakova, Alexandra
Zhernakova, Dasha V.
van Dongen, Jenny
Hottenga, Jouke J.
Pool, René
Isaacs, Aaron
Hofman, Bert A.
Jhamai, Mila
van der Kallen, Carla J.H.
Schalkwijk, Casper G.
Stehouwer, Coen D.A.
van den Berg, Leonard H.
van Galen, Michiel
Vermaat, Martijn
van Rooij, Jeroen
Uitterlinden, André G.
Verbiest, Michael
Verkerk, Marijn
Kielbasa, P. Szymon M.
Bot, Jan
Nooren, Irene
van Dijk, Freerk
Swertz, Morris A.
van Heemst, Diana
Relton, Caroline
Mill, Jonathan
Waldenberger, Melanie
Bell, Jordana T.
Jansen, Rick
Boomsma, D.I.
Dokumenttyp: Artikel
Erscheinungsdatum: 2018
Reihe/Periodikum: Luijk , R , Wu , H , Ward-Caviness , C K , Hannon , E , Carnero-Montoro , E , Min , J L , Mandaviya , P , Müller-Nurasyid , M , Mei , H , van der Maarel , S M , Beekman , M , der Breggen , R V , Deelen , J , Lakenberg , N , Moed , M , Suchiman , H E D , Arindrarto , W , van’t Hof , P , Jan Bonder , M , Deelen , P , Tigchelaar , E F , Zhernakova , A , Zhernakova , D V , van Dongen , J , Hottenga , J J , Pool , R , Isaacs , A , Hofman , B A , Jhamai , M , van der Kallen , C J H , Schalkwijk , C G , Stehouwer , C D A , van den Berg , L H , van Galen , M , Vermaat , M , van Rooij , J , Uitterlinden , A G , Verbiest , M , Verkerk , M , Kielbasa , P S M , Bot , J , Nooren , I , van Dijk , F , Swertz , M A , van Heemst , D , Relton , C , Mill , J , Waldenberger , M , Bell , J T , Jansen , R , Boomsma , D I & BIOS Consortium 2018 , ' Autosomal genetic variation is associated with DNA methylation in regions variably escaping X-chromosome inactivation ' , Nature Communications , vol. 9 , no. 1 , 3738 , pp. 1-9 . https://doi.org/10.1038/s41467-018-05714-3
Schlagwörter: /dk/atira/pure/keywords/cohort_studies/netherlands_twin_register_ntr_ / name=Netherlands Twin Register (NTR) / /dk/atira/pure/sustainabledevelopmentgoals/life_below_water / name=SDG 14 - Life Below Water
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27229190
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://research.vu.nl/en/publications/5788248b-a115-44b5-885d-ce6bb860af1a

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.