A multi-omic analysis of birthweight in newborn cord blood reveals new underlying mechanisms related to cholesterol metabolism

Rossella Alfano, Marc Chadeau-Hyam, Akram Ghantous, Pekka Keski-Rahkonen, Leda Chatzi, Almudena Espin Perez, Zdenko Herceg, Manolis Kogevinas, Theo M. de Kok, Tim S. Nawrot, Alexei Novoloaca, Chirag J. Patel, Costanza Pizzi, Nivonirina Robinot, Franca Rusconi, Augustin Scalbert, Jordi Sunyer, Roel Vermeulen, Martine Vrijheid, Paolo VineisOliver Robinson, Michelle Plusquin*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Birthweight reflects in utero exposures and later health evolution. Despite existing studies employing high-dimensional molecular measurements, the understanding of underlying mechanisms of birthweight remains limited.

Methods: To investigate the systems biology of birthweight, we (Toss-sectionally integrated the methylome, the transcriptome, the metabolome and a set of inflammatory proteins measured in cord blood samples, collected from four birth-cohorts (n = 489). We focused on two sets of 68 metabolites and 903 CpGs previously related to birthweight and investigated the correlation structures existing between these two sets and all other omic features via bipartite Pearson correlations.

Results: This dataset revealed that the set of metabolome and methylome signatures of birthweight have seven signals in common, including three metabolites [PC(34:2), plasmalogen PC(36:4)/PC(0-36:5), and a compound with m/z of 781.0545], two CpGs (on the DHCR24 and SC4MOL gene), and two proteins (periostin and CCL22). CCL22, a macrophage-derived chemokine has not been previously identified in relation to birthweight. Since the results of the omics integration indicated the central role of cholesterol metabolism, we explored the association of cholesterol levels in cord blood with birthweight in the ENVIRONAGE cohort (n 1097), finding that higher birthweight was associated with increased high-density lipoprotein cholesterol and that high-density lipoprotein cholesterol was lower in small versus large for gestational age newborns.

Conclusions: Our data suggests that an integration of different omic-layers in addition to single omics studies is a useful approach to generate new hypotheses regarding biological mechanisms. CCL22 and cholesterol metabolism in cord blood play a mechanistic role in birthweight. Crown Copyright (C) 2020 Published by Elsevier Inc.

Original languageEnglish
Article number154292
Number of pages12
JournalMetabolism-Clinical and Experimental
Publication statusPublished - Sept 2020


  • Birth weight
  • Cholesterol
  • DNA methylation
  • Gene expression
  • Metabolome
  • Proteins

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