title: The Role of Vitamin D in the Transcriptional Program of Human Pregnancy.
abstract: BACKGROUND
  Patterns of gene expression of human pregnancy are poorly understood. In a trial of vitamin D supplementation in pregnant women, peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks.
  
  
  OBJECTIVE
  Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life, yet the underlying mechanisms have not been examined. In this study, we used a network-based approach to examine changes in gene expression profiles during the course of normal pregnancy and evaluated their association with maternal Vitamin D levels.
  
  
  METHODS
  The VDAART study is a randomized clinical trial of vitamin D supplementation in pregnancy for reduction of pediatric asthma risk. The trial enrolled 881 women at 10-18 weeks of gestation. Longitudinal gene expression measures were obtained on thirty pregnant women, using RNA isolated from peripheral blood samples obtained in the first and third trimesters. Differentially expressed genes were identified using significance of analysis of microarrays (SAM), and clustered using a weighted gene co-expression network analysis (WGCNA). Gene-set enrichment was performed to identify major biological pathways.
  
  
  RESULTS
  Comparison of transcriptional profiles between first and third trimesters of pregnancy identified 5839 significantly differentially expressed genes (FDR<0.05). Weighted gene co-expression network analysis clustered these transcripts into 14 co-expression modules of which two showed significant correlation with maternal vitamin D levels. Pathway analysis of these two modules revealed genes enriched in immune defense pathways and extracellular matrix reorganization as well as genes enriched in notch signaling and transcription factor networks.
  
  
  CONCLUSIONS
  Our data show that gene expression profiles of healthy pregnant women change during the course of pregnancy and suggest that maternal Vitamin D levels influence transcriptional profiles. These alterations of the maternal transcriptome may contribute to fetal immune imprinting and reduce allergic sensitization in early life.
  
  
  BACKGROUND
  clinicaltrials.gov NCT00920621.
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Amal
authors.initials: A
authors.lastname: Al-Garawi
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Divya
authors.initials: D
authors.lastname: Chhabra
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Hooman
authors.identifier: http://orcid.org/0000-0002-2290-4436
authors.initials: H
authors.lastname: Mirzakhani
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Jarrett
authors.initials: J
authors.lastname: Morrow
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lasky-Su
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: Laranjo
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
authors.affiliation: Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
mesh_terms: D000328:Adult; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D011247:Pregnancy; D014158:Transcription, Genetic / Q000187:drug effects*; D059467:Transcriptome / Q000187:drug effects*; D014807:Vitamin D / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D014807:Vitamin D