The early-life exposome modulates the effect of polymorphic inversions on DNA methylation

Polymorphic genomic inversions are chromosomal variants with intrinsic variability that play important roles in evolution, environmental adaptation, and complex traits. We investigated the DNA methylation patterns of three common human inversions, at 8p23.1, 16p11.2, and 17q21.31 in 1,009 blood samp...

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Detalles Bibliográficos
Autores: Carreras-Gallo, Natàlia|||0000-0001-8559-2313, Cáceres, Alejandro|||0000-0001-8551-6695, Balagué Dobón, Laura|||0000-0003-3869-9737, Ruiz-Arenas, Carlos|||0000-0002-6014-3498, Andrusaityte, Sandra|||0000-0002-4309-0208, Carracedo, Ángel|||0000-0003-1085-8986, Casas, Maribel, Chatzi, Leda, Grazuleviciene, Regina|||0000-0002-0210-8053, Gutzkow, Kristine Bjerve, Lepeule, Johanna|||0000-0001-8907-197X, Maitre, Léa|||0000-0003-3682-7117, Nieuwenhuijsen, Mark|||0000-0001-9461-7981, Slama, Remy, Stratakis, Nikos, Thomsen, Cathrine, Urquiza, Jose|||0000-0003-2220-607X, Wright, John|||0000-0001-9572-7293, Yang, Tiffany, Escaramís, Geòrgia, Bustamante, Mariona|||0000-0003-0127-2860, Vrijheid, Martine|||0000-0002-7090-1758, Pérez-Jurado, Luis Alberto|||0000-0002-1988-3005, González, Juan Ramón|||0000-0003-3267-2146
Tipo de recurso: artículo
Fecha de publicación:2022
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:293096
Acceso en línea:https://ddd.uab.cat/record/293096
https://dx.doi.org/urn:doi:10.1038/s42003-022-03380-2
Access Level:acceso abierto
Palabra clave:DNA methylation
Genetic interaction
Risk factors
Descripción
Sumario:Polymorphic genomic inversions are chromosomal variants with intrinsic variability that play important roles in evolution, environmental adaptation, and complex traits. We investigated the DNA methylation patterns of three common human inversions, at 8p23.1, 16p11.2, and 17q21.31 in 1,009 blood samples from children from the Human Early Life Exposome (HELIX) project and in 39 prenatal heart tissue samples. We found inversion-state specific methylation patterns within and nearby flanking each inversion region in both datasets. Additionally, numerous inversion-exposure interactions on methylation levels were identified from early-life exposome data comprising 64 exposures. For instance, children homozygous at inv-8p23.1 and higher meat intake were more susceptible to TDH hypermethylation (P = 3.8 × 10 -22); being the inversion, exposure, and gene known risk factors for adult obesity. Inv-8p23.1 associated hypermethylation of GATA4 was also detected across numerous exposures. Our data suggests that the pleiotropic influence of inversions during development and lifetime could be substantially mediated by allele-specific methylation patterns which can be modulated by the exposome. Analysis of the relationship between presence of common DNA sequence inversions and DNA methylation patterns suggests a role for environmental exposures (such as food intake) in mediating inversion state-specific methylation patterns.

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