Placental multi-omics integration identifies candidate functional genes for birthweight.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 05 2022
02 05 2022
Historique:
received:
14
08
2021
accepted:
11
04
2022
entrez:
2
5
2022
pubmed:
3
5
2022
medline:
6
5
2022
Statut:
epublish
Résumé
Abnormal birthweight is associated with increased risk for cardiometabolic diseases in later life. Although the placenta is critical to fetal development and later life health, it has not been integrated into largescale functional genomics initiatives, and mechanisms of birthweight-associated variants identified by genome wide association studies (GWAS) are unclear. The goal of this study is to provide functional mechanistic insight into the causal pathway from a genetic variant to birthweight by integrating placental methylation and gene expression with established GWAS loci for birthweight. We identify placental DNA methylation and gene expression targets for several birthweight GWAS loci. The target genes are broadly enriched in cardiometabolic, immune response, and hormonal pathways. We find that methylation causally influences WNT3A, CTDNEP1, and RANBP2 expression in placenta. Multi-trait colocalization identifies PLEKHA1, FES, CTDNEP1, and PRMT7 as likely functional effector genes. These findings reveal candidate functional pathways that underpin the genetic regulation of birthweight via placental epigenetic and transcriptomic mechanisms. Clinical trial registration; ClinicalTrials.gov, NCT00912132.
Identifiants
pubmed: 35501330
doi: 10.1038/s41467-022-30007-1
pii: 10.1038/s41467-022-30007-1
pmc: PMC9061712
doi:
Substances chimiques
PRMT7 protein, human
EC 2.1.1.319
Protein-Arginine N-Methyltransferases
EC 2.1.1.319
CTDNEP1 protein, human
EC 3.1.3.16
Phosphoprotein Phosphatases
EC 3.1.3.16
Banques de données
ClinicalTrials.gov
['NCT00912132']
Types de publication
Clinical Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, American Recovery and Reinvestment Act
Research Support, N.I.H., Intramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2384Subventions
Organisme : Medical Research Council
ID : MC_PC_17228
Pays : United Kingdom
Organisme : NICHD NIH HHS
ID : HHSN275201000009C
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275200800028C
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275200800012C
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275200800014C
Pays : United States
Organisme : NIEHS NIH HHS
ID : R24 ES028507
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275200800013C
Pays : United States
Organisme : Medical Research Council
ID : MC_QA137853
Pays : United Kingdom
Organisme : NIEHS NIH HHS
ID : R01 ES022223
Pays : United States
Organisme : NICHD NIH HHS
ID : R00 HD097286
Pays : United States
Organisme : NICHD NIH HHS
ID : HHSN275200800002I
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR002539
Pays : United States
Informations de copyright
© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.
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