RESUMO
BACKGROUND: While stress and the absence of social support during pregnancy have been linked to poor health outcomes, the underlying biological mechanisms are unclear. METHODS: We examined whether adverse experiences during pregnancy alter DNA methylation (DNAm) in maternal epigenomes. Analyses included 250 African-American mothers from the Boston Birth Cohort. Genome-wide DNAm profiling was performed in maternal blood collected after delivery, using the Infinium HumanMethylation450 Beadchip. Linear regression models, with adjustment of pertinent covariates, were applied. RESULTS: While self-reported maternal psychosocial lifetime stress and stress during pregnancy was not associated with DNAm alterations, we found that absence of support from the baby's father was significantly associated with maternal DNAm changes in TOR3A, IQCB1, C7orf36, and MYH7B and that lack of support from family and friends was associated with maternal DNA hypermethylation on multiple genes, including PRDM16 and BANKL. CONCLUSIONS: This study provides intriguing results suggesting biological embedding of social support during pregnancy on maternal DNAm, warranting additional investigation, and replication.
Assuntos
Metilação de DNA , Apoio Social , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenosina Trifosfatases/genética , Adulto , Negro ou Afro-Americano , Boston , Proteínas de Ligação a Calmodulina/genética , Miosinas Cardíacas/genética , Ilhas de CpG , Proteínas de Ligação a DNA/genética , Epigenoma , Epigenômica , Pai , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Proteínas de Membrana/genética , Antígenos de Histocompatibilidade Menor/genética , Chaperonas Moleculares/genética , Mães , Cadeias Pesadas de Miosina/genética , Avaliação de Resultados em Cuidados de Saúde , Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etnologia , Estudos Retrospectivos , Classe Social , Fatores de Transcrição/genética , População Urbana , Adulto JovemRESUMO
MOTIVATION: Tiling array is a new type of microarray that can be used to survey genomic transcriptional activities and transcription factor binding sites at high resolution. The goal of this paper is to develop effective statistical tools to identify genomic loci that show transcriptional or protein binding patterns of interest. RESULTS: A two-step approach is proposed and is implemented in TileMap. In the first step, a test-statistic is computed for each probe based on a hierarchical empirical Bayes model. In the second step, the test-statistics of probes within a genomic region are used to infer whether the region is of interest or not. Hierarchical empirical Bayes model shrinks variance estimates and increases sensitivity of the analysis. It allows complex multiple sample comparisons that are essential for the study of temporal and spatial patterns of hybridization across different experimental conditions. Neighboring probes are combined through a moving average method (MA) or a hidden Markov model (HMM). Unbalanced mixture subtraction is proposed to provide approximate estimates of false discovery rate for MA and model parameters for HMM. AVAILABILITY: TileMap is freely available at http://biogibbs.stanford.edu/~jihk/TileMap/index.htm. SUPPLEMENTARY INFORMATION: http://biogibbs.stanford.edu/~jihk/TileMap/index.htm (includes coloured versions of all figures).