DNA methylation changes in cord blood and the developmental origins of health and disease – a systematic review and replication study

BMC Genomics

for the NutriGen Alliance¹  Padmaja Subbarao²  Meghan B Azad³  Stuart E Turvey⁴  Theo J Moraes⁵  Piush J Mandhane⁶  Loubna Akhabir⁷  Randa Stringer⁷  Sonia S. Anand⁷  Guillaume Paré⁷  Dipika Desai⁷ 

[1] ;Department of Medicine, McMaster University;Department of Pediatrics and Child Health, Children’s Hospital Research Institute of Manitoba, University of Manitoba;Department of Pediatrics, BC Children’s Hospital, University of British Columbia;Department of Pediatrics, Hospital for Sick Children;Department of Pediatrics, University of Alberta;Population Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute;

关键词: Cord blood;    methylation;    EWAS;    prenatal;    In utero;    CHILD;    START;    Nutrigen;   

DOI  :  10.1186/s12864-022-08451-6

来源: DOAJ

【 摘 要 】

Abstract Background Environmental exposures in utero which modify DNA methylation may have a long-lasting impact on health and disease in offspring. We aimed to identify and replicate previously published genomic loci where DNA methylation changes are attributable to in utero exposures in the NutriGen birth cohort studies Alliance. Methods We reviewed the literature to identify differentially methylated sites of newborn DNA which are associated with the following five traits of interest maternal diabetes, pre-pregnancy body mass index (BMI), diet during pregnancy, smoking, and gestational age. We then attempted to replicate these published associations in the Canadian Healthy Infant Longitudinal Development (CHILD) and the South Asian birth cohort (START) cord blood epigenome-wide data. Results We screened 68 full-text articles and identified a total of 17 cord blood epigenome-wide association studies (EWAS) of the traits of interest. Out of the 290 CpG sites reported, 19 were identified in more than one study; all of them associated with maternal smoking. In CHILD and START EWAS, thousands of sites associated with gestational age were identified and maintained significance after correction for multiple testing. In CHILD, there was differential methylation observed for 8 of the published maternal smoking sites. No other traits tested (i.e., folate levels, gestational diabetes, birthweight) replicated in the CHILD or START cohorts. Conclusions Maternal smoking during pregnancy and gestational age are strongly associated with differential methylation in offspring cord blood, as assessed in the EWAS literature and our birth cohorts. There are a limited number of reported methylation sites associated in more than two independent studies related to pregnancy. Additional large studies of diverse populations with fine phenotyping are needed to produce robust epigenome-wide data in order to further elucidate the effect of intrauterine exposures on the infants’ methylome.

【 授权许可】

Unknown