DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins

TY - JOUR

T1 - DNA Methylation Changes in the IGF1R Gene in Birth Weight Discordant Adult Monozygotic Twins

AU - Tsai, Pei Chien

AU - Van Dongen, Jenny

AU - Tan, Qihua

AU - Willemsen, Gonneke

AU - Christiansen, Lene

AU - Boomsma, Dorret I.

AU - Spector, Tim D.

AU - Valdes, Ana M.

AU - Bell, Jordana T.

PY - 2015/12

Y1 - 2015/12

N2 - 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.

AB - 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.

KW - birth weight

KW - discordant monozygotic twin pairs

KW - epigenome-wide association scans

UR - http://www.scopus.com/inward/record.url?scp=84946771261&partnerID=8YFLogxK

U2 - 10.1017/thg.2015.76

DO - 10.1017/thg.2015.76

M3 - Article

SN - 1832-4274

VL - 18

SP - 635

EP - 646

JO - TWIN RESEARCH AND HUMAN GENETICS

JF - TWIN RESEARCH AND HUMAN GENETICS

IS - 6

ER -