title: DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins.
abstract: Low birth weight (LBW) can have an impact on health outcomes in later life, especially in relation to pre-disposition to metabolic disease. Several studies suggest that LBW resulting from restricted intrauterine growth leaves a footprint on DNA methylation in utero, and this influence likely persists into adulthood. To investigate this further, we performed epigenome-wide association analyses of blood DNA methylation using Infinium HumanMethylation450 BeadChip profiles in 71 adult monozygotic (MZ) twin pairs who were extremely discordant for birth weight. A signal mapping to the IGF1R gene (cg12562232, p = 2.62 × 10(-8)), was significantly associated with birth weight discordance at a genome-wide false-discovery rate (FDR) of 0.05. We pursued replication in three additional independent datasets of birth weight discordant MZ pairs and observed the same direction of association, but the results were not significant. However, a meta-analysis across the four independent samples, in total 216 birth-weight discordant MZ twin pairs, showed a significant positive association between birth weight and DNA methylation differences at IGF1R (random-effects meta-analysis p = .04), and the effect was particularly pronounced in older twins (random-effects meta-analysis p = .008, 98 older birth-weight discordant MZ twin pairs). The results suggest that severe intra-uterine growth differences (birth weight discordance >20%) are associated with methylation changes in the IGF1R gene in adulthood, independent of genetic effects.
authors.affiliation: Department of Twin Research & Genetic Epidemiology,King's College London,London,UK.
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Jenny
authors.initials: J
authors.lastname: Van Dongen
authors.affiliation: Epidemiology, Biostatistics and Biodemography,Institute of Public Health,University of Southern Denmark,Denmark.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.affiliation: Epidemiology, Biostatistics and Biodemography,Institute of Public Health,University of Southern Denmark,Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
authors.affiliation: Department of Biological Psychology,VU University Amsterdam,Amsterdam,the Netherlands.
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.affiliation: Department of Twin Research & Genetic Epidemiology,King's College London,London,UK.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Twin Research & Genetic Epidemiology,King's College London,London,UK.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.affiliation: Department of Twin Research & Genetic Epidemiology,King's College London,London,UK.
authors.forename: Jordana T
authors.initials: JT
authors.lastname: Bell
mesh_terms: D000328:Adult; D000368:Aged; D001724:Birth Weight / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017526:Receptor, IGF Type 1; D017451:Receptors, Somatomedin / Q000235:genetics*; D014430:Twins, Monozygotic / Q000235:genetics*; D055815:Young Adult
chemical_list: C000597236:IGF1R protein, human; D017451:Receptors, Somatomedin; D017526:Receptor, IGF Type 1
keywords: birth weight; discordant monozygotic twin pairs; epigenome-wide association scans